Category Archives: Nano medicine

Introduction

Over the last decades, personalized medicine has greatly evolved with the development of imaging tools that improve the management of several diseases, especially cancer.1 Among all the non-invasive imaging techniques, the nuclear imaging modalities Single Photon Emission Computed Tomography (SPECT) and Positron Emission Tomography (PET) stand out mainly due to their high sensitivity prospect of obtaining quantitative information. In fact, PET and SPECT imaging can provide detailed information about the in vivo behavior and pharmacokinetics of several compounds, such as nanomedicines, and can facilitate their translation to clinics.2

On the other hand, nanomedicine has emerged as a promising strategy to improve diagnosis and treatment of prevalent diseases including cancer.3,4 One of the most promising advantages of nanomedicine is the possibility to combine therapeutic molecules with diagnostic agents into single multifunctional nanoparticles, known as nanotheranostics, opening an entirely new field of development towards the implementation of personalized medicine.5,6 In recent years, the combination of nanoparticles with radionuclides is rapidly growing and there are a great number of submissions for the Food and Drug Administration approval.7 Different types of nanoparticles are investigated for nuclear medicine applications and multimodal imaging.8 For example, inorganic nanoparticles have been widely studied due to their intrinsic physical properties, that convert them into materials with a high potential for multimodal imaging.9,10 Nevertheless, organic nanoparticles are still the most in demand for the development of imaging probes by virtue of their biodegradable and biocompatible composition, preventing a long-term accumulation in the body and undesirable toxic side effects.11 Indeed, liposomes are the most extended type of organic nanoparticles for nuclear imaging applications. Liposomes can be radiolabeled by different methodologies, which can be adapted to different kinds of nanoparticles, such as micelles, solid lipid nanoparticles, and nanoemulsions.12 Chelator-based radiolabeling strategies offer a high versatility for the incorporation of radionuclides with different properties, suitable for complementary imaging techniques and nanotheranostics.13

Nanoemulsions are defined as nanoscale droplets in which two immiscible liquids are mixed to form a single phase. Their biocompatible composition, easy production by soft and scalable methodologies and improved drug loading capacity compared to liposomes, are relevant advantages that have prompted their use in biomedicine.14,15

Nanoemulsions have been widely studied for fluorescence, MRI and ultrasounds imaging.16,17 However, their use in nuclear imaging is still recent and there are only few reports describing radiolabeled nanoemulsions.1820 Our group has recently reported the development and characterization of sphingomyelin nanoemulsions that incorporate sphingomyelin, one of the main lipids in cell membranes (SNs), and claimed their potential in drug delivery.21 The principal advantages of SNs relate to their safe and simple composition, long-term colloidal stability, and capacity for accommodation of different types of functionalities and therapeutic payloads.2123 Previous attempts by our research group have proved that SNs can be radiolabeled with Fluorine-18 for PET imaging following a maleimide reaction. However, radiochemical yields (RCY) were found to be highly dependent on the crosslinking efficacy.24 The aim of this work was to provide an optimized composition and straightforward methodology for the radiolabeling of SNs with 68Ga and 67Ga radioisotopes using a chelator-based strategy. Radiolabeled formulations can be used for indistinct application in PET and SPECT imaging, and therefore adaptable to specific needs and biomedical applications.

Octadecylamine (stearylamine, >99%, Merck Group, Darmstadt, Germany) was conjugated to 2-(4-isothiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid (p-SCN-Bn-NOTA, NOTA, >94%, Macrocyclics, Dallas, TX, USA) to obtain a lipid derivative chelator for further inclusion into the nanoemulsions. Details about the reaction protocol and the product characterization are included in the Supporting Information.

SNs were prepared following a method previously reported by our group with minor modifications.21 Briefly, oleic acid (5 mg, 6588%, Merck Group, Darmstadt, Germany), egg sphingomyelin (0.5 mg, 98%, Lipoid GmbH, Ludwigshafen, Germany) and the surfactant C16/C18-COO-C9H9O3 (0.5 mg, 96%, GalChimia S.L, A Corua, Spain) with a lipid ratio 1:0.1:0.1 w/w were dissolved in 100 L of absolute ethanol (99.7%, Cienytech S.L., A Corua, Spain). All the additional lipid derivatives used to functionalize SNs, such us 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine-N-diethylenetriaminepentaacetic acid (DTPA, 0.05 mg, >99%, Avanti Polar Lipids, Alabama, Al, USA), NOTA (0.05 mg) or an oleic acid modified polyethylene glycol (PEG, 2 kDa, 0.125 mg, Nanocs, New York, NY, USA) were included in the organic phase. Then, this organic phase was injected in 1 mL of MilliQ water (Millipore Milli-Q system) under magnetic stirring using an insulin syringe (0.5 mL, 0.3312 mm ICO.C.1) and nanoemulsions (SNs, DTPA-SNs, NOTA-SNs or NOTA-PEG-SNs) were spontaneously formed. To prepare SNs coated with hyaluronic acid (NOTA-HA-SNs), the organic phase containing the lipids and NOTA was injected under stirring in 1 mL of an aqueous solution of sodium hyaluronate (HA, 170 kDa, 2 mg mL1, >95%, Bioiberica, S.A.U, Barcelona, Spain).

All the nanoemulsions were physiochemically characterized using a Nanosizer 2000 (Malvern Instruments, Malvern, UK). The mean size and its distribution, defined by the polydispersity index (PDI), were measured by Dynamic Light Scattering (DLS). Measurements were performed on disposable microcuvettes (ZEN0040, Malvern Instruments) upon dilution of the SNs in MilliQ water, reaching a final lipid concentration of 0.5 mg mL1. The zeta potential (ZP) was analyzed by Laser Doppler Anemometry (LDA) diluting SNs in MilliQ water (lipid concentration 0.12 mg mL1) with Folded capillary cuvettes (DTS1070, Malvern Instruments). The stability of SNs, DTPA-SNs and NOTA-SNs was tested under storage conditions at 4 C up to one month and also after incubation with human serum at 37 C for 72 h. The colloidal properties were measured by DLS maintaining the conditions mentioned before. Parameters such as the medium (water) and the temperature (25C) were fixed for all the measurements.

The morphology of SNs was observed by Field Emission Scanning Electron Microscopy (FESEM) using a ZEISS FESEM ULTRA Plus, microscope (Carl Zeiss Micro Imaging, GmbH, Germany). Before the measurement, 20 L of sphingomyelin nanoemulsions (0.5 mg mL1) were stained with 20 L phosphotungstic acid (2% w/v). Then, 20 L of the mixture was placed on a carbon coated grid and left for 2 minutes. The excess was removed using a filter paper and the grid was allowed to dry. The grid was washed 5 times with 100 L of filtered MilliQ water and it was dried overnight.

A549 (ATCC CCL-185), MDA-MB-231 (ATCC HTB-26) were cultured in Dulbeccos modified Eagles medium high glucose (DMEM, Merck Group, Darmstadt, Germany) and OMM-2.5 (kindly provided by Martine J. Jager from Leiden University Medical Center, Leiden, The Netherlands) were grown in RPMI (Gibco, Thermo Scientific S.L., Waltham, MA, United States). Both media were supplemented with 10% fetal bovine serum (FBS) and 1% penicillin:streptomycin (Gibco, Thermo Scientific S.L., Waltham, MA, United States). Cells were maintained at 37 C with 95% relative humidity and 5% CO2.

Cellular uptake of SNs was studied by confocal microscopy. 8104 cells/well were seeded in an 8-well -chamber (SPL Life Sciences Co., Ltd., Gyeonggi-do, Korea). After 24 h, cells were treated with SNs (0.13 mg mL1 per well) labeled with C11-TopFluor sphingomyelin (>99%, Avanti Polar Lipids, Alabama, Al, USA). After 4 h of incubation at 37 C, cells were washed with 1x phosphate buffer saline (PBS) twice and fixed with 4% paraformaldehyde for 15 min. Cells were then washed twice with 1x PBS and the cellular nuclei were counterstained with Hoechst 33,342 (Thermo Scientific S.L., Waltham, MA, United States) for 5 min. After washing, the slide was mounted with Mowiol (Merck Group, Darmstadt, Germany) and a coverslip. The samples were left to dry in the dark overnight at RT, following their storage at 20 C, until taken for observation under a confocal microscope (Confocal Laser Microscope Leica SP8).

68Ga (t = 68 min, + = 89% and EC = 11%) was obtained from a 68Ge/68Ga generator system (ITG Isotope Technologies Garching GmbH, Germany) in which 68Ge (t = 270 d) was attached to a column based on an organic matrix generator. The 68Ga was eluted with 4 mL of 0.05 M hydrochloric acid. Then, 500 L of DTPA-SNs or NOTA-SNs (13 mg mL1) were mixed with 500 L of 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid buffer (HEPES, 0.5 M, pH 5.05). The mixture was incubated with 1.5 mL of 68Ga (300 MBq) at 30 C for 30 min and purified by PD-10 columns. The incorporated radioactivity was measured in an activimeter (AtomLabTM500, Biodex).

67Ga-citrate (t = 78.3 h, 100% EC = 39% 93 keV, 21% 185 keV, 17% 300 keV) was obtained from CURIUM (France) as sterile solution with a pH between 5 and 8 and a radiochemical purity at least equal to 95%. 67Ga-citrate solution was converted to 67GaCl3 using a method previously described.25 In brief, 2 mL of 67Ga-citrate (37 MBq) diluted in distilled water was filtered with a SEP-PAK Plus silica cartridge (ABX, Advanced Biochemical Compounds, Germany) using a 5 mL plastic syringe. Afterwards, the silica cartridge was washed three times with 5 mL of distilled water to remove the free citrate ions. The 67Ga3+ ions were eluted with 3 mL of HCl 0.1 M, obtaining a solution of 67GaCl3 which was concentrated on a rotary vacuum evaporator to get a final volume of 500 L. The pH was adjusted to 45 with NaOH 0.1 M and the solution was incubated with 500 L of NOTA-SNs, NOTA-HA-SNs or NOTA-PEG-SNs (10 mg mL1) diluted in HEPES buffer (1.5 M, pH 5.05) for 1 h at 37 C. The labeled nanoemulsions were eventually purified with PD-10 columns and the radioactivity was measured in the activimeter.

The radiochemical yield (RCY) was calculated as a percentage of decay corrected activity found in the post-purification solution compared to the starting activity. The radiochemical stability (RCS) of 68Ga-labeled nanoemulsions was assessed by incubating the emulsions with animal serum at 37 C for 4 hours. In case of 67Ga-labeled nanoemulsions, the stability was measured after incubation with animal serum for 0, 24, 48 and 72 h, according to the acquisition time points. In both cases, after the incubation time the mixture was purified by a PD-10 column and the activity of the elution was measured and decay corrected. Radiochemical purity (RCP) was analyzed by instant thin-layer chromatography (ITLC), and details regarding experimental protocols are included in the Supporting Information.

In vivo PET/CT imaging was performed in healthy mice (C57BL/6) with a nanoPET/CT small-animal imaging system (Mediso Medical Imaging Systems, Budapest, Hungary). List-mode PET data acquisition commenced 2 hours post bolus injection of ~12 MBq of 68Ga-DTPA-SNs or 68Ga-NOTA-SNs (12 MBq, n = 5) through the tail vein and continued for 30 minutes. At the end of PET, microCT was performed for attenuation correction and anatomic reference. The dynamic PET images in a 105105 matrix (frame rates: 310 min, 130 min, 160 min) were reconstructed using a Tera-Tomo 3D iterative algorithm. Acquisition and reconstruction were performed with proprietary Nucline software (Mediso, Budapest, Hungary). Qualitative Image analysis in mice was performed using Osirix software (Pixmeo, Switzerland). Animal experiments were conducted according to the ethical and animal welfare committee at CNIC and the Spanish and UE legislation. Experimental protocols have been approved by Madrid regional government (PROEX16/277).

SPECT studies were carried out on male SpragueDawley rats with an average weight of 299.5 23.45 g supplied by the animal facility at the University of Santiago de Compostela (Spain). Planar dynamic SPECT images were acquired with a single-head clinical Siemens Orbiter gamma camera (Siemens Medical Solutions, Inc., USA) using a parallel collimator specifically designed for low-energy photons and high spatial resolution. Data were acquired in list-mode format in order to apply energy and spatial linearity, and uniformity corrections. In vivo NOTA-SNs and free 67Ga biodistribution were studied after the intravenous injection (17.70 8.5 MBq, n = 5) in healthy rats at different time-points: 24, 48 and 72 h. In order to compare the differences in biodistribution between NOTA-SNs, HA-SNs and PEG-SNs, healthy rats were intravenously injected (13.2 0.3 MBq, n = 3) and the images were acquired dynamically during the first 60 min after injection (30 frames/2min). All images were analyzed using AMIDE software (amide.sourceforge.net). Quantitative analysis was carried out in a dynamic study by using circularly delineated Regions of Interest (ROIs) in the heart and liver, with 9 mm in diameter. The mean uptake was calculated over time in every region averaged over each of the 3 frames (6 min) and the results were reported as heart-to-liver ratio.

Ex vivo biodistribution of 68Ga-labeled nanoemulsions was conducted 4 h post-injection. In case of 67Ga-labeled nanoemulsions, biodistribution studies were performed 72 h post-injection. Animals were sacrificed in a CO2 chamber, organs were extracted and counted with a Wizard 1470 gamma counter (Perkin Elmer) for 1 min each (n=5 per experiment). Radioactivity decay was corrected, and a biodistribution was presented as the percentage of injected dose per gram (% ID/g).

All the experiments were performed at least in triplicate. Data are expressed as mean standard deviation (SD). Statistical analyses were calculated using GraphPad Prism software (version 8.0). Students t-test was used to compare significant differences between the two groups. * (p0.05), ** (p0.01), ***(p0.001)was considered statistically significant.

Here, we describe the radiolabeling of SNs with Gallium-68 and Gallium-67 for their application in PET and SPECT imaging. SNs were prepared by ethanol injection, a one-step mild technique that allows obtaining colloidal nanoemulsions within seconds (Figure 1A, left). The reproducibility of the preparation method (Figure 1A, right) was obtained after measuring 24 independent batches by DLS (raw data are showed in Table S1). SNs showed spherical morphology, as observed in FESEM images (Figure 1B). Additionally, SNs were efficiently internalized in cancer cells (Figure 1C), which is a relevant factor to take into account in order to determine the potential of a formulation for biomedicine applications. Stability determinations in cell culture media were also performed and are shown in Figure S1, Supporting Information. To convert SNs into suitable probes for PET and SPECT imaging, we followed a chelator-mediated approach, which is one of the most used methods to radiolabel nanoparticles with radionuclides, such as 64Cu, 68Ga, 99mTc or 111In.13,26 Labeling organic nanoparticles, and especially lipid nanoparticles, can be done by the use of lipid-derivative chelators. These conjugates can be inserted into the membrane of the lipid particles at the time of their preparation.2729 In this study, we used two different lipid-derivative chelators to determine the best candidate for in vivo imaging. First, we selected the acyclic chelator diethylenetriaminepentaacetic acid modified with a dimyristoyl-sn-glycero-3-phosphoethanolamine chain (DTPA). Second, we synthesized the amphiphilic derivative of the macrocyclic chelator 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) as previously described.3032 In brief, a stearylamine was reacted with the isothiocyanate macrocycle p-SCN-Bn-NOTA (1, Figure S2A, Supporting Information). The nucleophilic substitution in N,N-dimethylformamide afforded the corresponding thiourea derivative (2, NOTA-stearylamine, Figure S2A, Supporting Information) after recrystallization at moderate yield (23%). The NOTA-stearylamine derivative 2 was characterized by high-resolution mass spectrometry (Figure S2B Supporting Information) and NMR, confirming its structure (Figures S3 and S4 Supporting Information). Both lipid-modified chelators were spontaneously incorporated into the lipidic layer of SNs. According to results shown in Table 1, a slight increase in size was observed for DTPA-SNs and NOTA-SNs with respect to the control SNs, which could be indicative of the efficient incorporation of the chelators. In all cases, we observed a narrow distribution of the particles with a PDI 0.2.

Table 1 Physicochemical Characterization of SNs, DTPA-SNs and NOTA-SNs Measured by DLS and LDA (Results are Expressed as Mean Standard Deviation, n = 3)

Figure 1 (A) Scheme of the one-step method used for the preparation of SNs (left) and the method reproducibility after measuring the hydrodynamic size of 24 independent batches by DLS (right); horizontal bars represent size mean and standard deviation (127 9 nm). (B) Representative Field Emission Scanning Electron Microscopy (FESEM) images of SNs acquired with STEM (top) and InLens (bottom) detectors. (C) Confocal microscopy images showing the internalization of SNs in different cancer cell lines. SNs are labeled in green (TopFluor-SM) and cell nuclei are labeled in blue (Hoechst).

Stability studies under storage conditions at 4 C showed that all the formulations were highly stable during the tested period (Figure 2A), indicating that the incorporation of the lipid-derivative chelators does not compromise the colloidal properties of SNs. In addition, they showed high stability in the human serum for 72 h at 37 C, as shown in Figure 2B, demonstrating their potential for in vivo applications. Although organic nanoparticles offer relevant advantages with respect to inorganic nanoparticles, in general, their preparation is still complex, as dendrimers, liposomes or nanogels tend to require multi-step preparation methods and/or typically the use of high-energy techniques. On the contrary, this methodology provides long-term stable DTPA-SNs and NOTA-SNs particles in few minutes through a one-step protocol. Moreover, the preparation of DTPA-SNs and NOTA-SNs avoids the use of high-energy techniques and uses low-cost and conventional starting materials. In fact, compared with previously reported organic nanosystems, we describe here the simplest and easiest methodology for the gallium radiolabeling through a chelator-based strategy.3335

Figure 2 (A) Storage stability of SNs, DTPA-SNs and NOTA-SNs at 4 C measuring the evolution of the average size by DLS for one month (n=3). (B) Stability in human serum at 37 C during 72 h measured by DLS (n=3). (C) Radiochemical yield of 68Ga-DTPA-SNs and 68Ga-NOTA-SNs after incubation with the radioisotope for 30 min at 30 C (n=3). (D) Radiochemical stability of 68Ga-SNs, 68Ga-DTPA-SNs and 68Ga-NOTA-SNs after incubation with serum 4 h at 37 C (n=3).

The combination of nanomaterials with 68Ga for PET imaging has attracted a great deal of attention in recent years with several works devoted to the radiolabeling of inorganic nanoparticles.36 However, only a few studies with organic nanoparticles, specifically PEGylated DTPA and NODAGA liposomes, PAMAM dendrimer-DOTA conjugates, NODAGA and DOTA nanogels, NODAGA polymeric nanoparticles and PSMA-DOTA microemulsions, have been reported so far.33,3741

DTPA-SNs, NOTA-SNs and non-chelator SNs (control) were radiolabeled by incubation with 68Ga3+ at 30 C for 30 min, and then purified by gel filtration in PD-10 columns. Figure 2C reveals that DTPA-SNs and NOTA-SNs were efficiently labeled with 68Ga, reaching RCY of 82 4% for DTPA-SNs and 92 2% for NOTA-SNs. Differences in RCY might be related to some release of 68Ga-DTPA-PE from the nanoemulsions in the purification process and/or to a better incorporation of the NOTA-SA derivative with SNs. With respect to the control formulation, nonspecific radiolabeling (RCY, 30 12%) was observed. This might be due to some entrapment of the radioisotope into the lipid membrane of the nanoemulsions mediated by electrostatic interactions. Radiochemical yields were in line with other works in the field, such as liposomes, nanogels, biopolymer nanoparticles and microemulsions.33,3941 The radiochemical purity was evaluated by ITLC using a sodium citrate solution as mobile phase. Under these conditions, free 68Ga showed a retention factor of 0.75 (Figure S5A, Supporting Information). In case of 68Ga-nanoemulsions, we could not detect the presence of free 68Ga, showing an RCP higher than 99% (Figure S5B, Supporting Information).

The RCS of the nanoemulsions upon incubation with serum at 37 C was also determined (Figure 2D). As expected, radiolabeled control SNs (without a chelator) were not able to retain the gallium. In the case of DTPA-SNs, only 50 3% of 68Ga were retained, while NOTA-SNs showed the highest stability, retaining 90 2% of activity, again in line with cyclic chelators as NODAGA or DOTA.37,39,40,42 On the other hand, although DTPA is commonly used to form complexes with gallium and other radioisotopes, the formation of less stable complexes can be a consequence of its acyclic structure.43 This was confirmed after intravenous injection of DTPA-SNs and NOTA-SNs (12 MBq, n = 5) to healthy mice. 3D PET/CT images were acquired 2 h post-administration and showed major accumulation in the reticuloendothelial system (RES) organs and heart (Figure 3A). As expected, DTPA-SNs showed a higher circulation in the bloodstream due to the premature release of the radionuclide from the nanoemulsion. Ex vivo biodistribution results were conducted 4 h post-injection (Figure 3B) and corroborate major liver and spleen accumulation. This is in concordance with the in vivo pattern observed for most of the nanoparticles, especially lipid nanoparticles, such as liposomes and nanoemulsions.19,24,37,44 Remarkably, NOTA-SNs have a relatively long circulation time, showing a 10% of the injected dose in the bloodstream 4 h after intravenous injection. This in vivo pattern differs from other 68Ga-labeled emulsions recently reported, with a shorter circulation half-life, mainly due to differences in size and composition.41 These results indicate that the pharmacokinetics of NOTA-SNs can be better studied after the radiolabeling with longer half-life radioisotopes, such as 67Ga. Nevertheless, NOTA-SNs could be surface decorated with specific biomolecules in order to reduce their circulation time and to perform suitable probes for targeted 68Ga molecular imaging.45

Figure 3 (A) Representative PET/CT whole-body coronal images of 68Ga-DTPA-SNs and 68Ga-NOTA-SNs biodistribution in healthy mice 2 h after intravenous injection (n=5). (B) Ex vivo biodistribution of both radiolabeled nanoemulsions 4 h post-injection (n=5). **(p0.01), ***(p0.001) was considered statistically significant.

67Ga, compared with 68Ga (t = 68 minutes), allowed a long-term biodistribution study of NOTA-SNs by SPECT imaging. For NOTA-SNs radiolabeling, the clinical formulation 67Ga-citrate was initially converted into the chloride form (GaCl3) as previously described.25 Briefly, 67Ga-citrate was trapped in a silica cartridge, washed with distilled water and finally eluted with HCl 0.1 M, rendering a 90% yield. To ensure a successful radiolabeling and taking into account that with the half-life of 67Ga there are no strong limitations for increasing the incubation time, we optimized the process (the solution was incubated with NOTA-SNs for 1 h at 37 C). Then, the free radionuclide was removed by filtration in PD-10 columns, obtaining a 80 2% of RCY (Figure 4A, before incubation with serum), between 10% and 20% higher than polymer and protein-based nanoparticles previously reported.34,46 The measured RCP was 98.9%, conducted by ITLC (Table S2, Supporting Information). In addition, RCS studies proved that the labeling was highly stable in serum over 72 h (Figure 4A). Then, due to the longer half-time of this radioisotope, SPECT studies were designed to evaluate the pharmacokinetics of NOTA-SNs at prolonged time periods. In vivo SPECT images were acquired 24, 48 and 72 h after intravenous injection of the radiolabeled NOTA-SNs. In parallel, we evaluated the in vivo uptake of the free radioisotope as a control. Animals injected with free 67Ga (control) showed uptake in the bloodstream, liver, lacrimal and salivary glands (Figure 4B), according previous reports.34,47 We can also observe free 67Ga in the bladder and kidneys, a consequence of renal clearance. In comparison, NOTA-SNs showed similar biodistribution than observed in PET/CT images, with main accumulation in liver and RES organs, and its intensity decreases over time. After 72 h, we measured the ex vivo biodistribution and observed that the radioactivity remained only in liver and spleen with less than 5% ID/g in both organs (Figure S6, Supporting Information). This could be related to the biodegradation of the particles and/or their excretion through the urine, in line with our previous report in which we described cationic fluorine-labeled nanoemulsions.24 However, further studies must be carried out to determine the excretion routes of NOTA-SNs.

Figure 4 (A) Radiochemical yield of 67Ga-NOTA-SNs (control) and radiochemical stability after incubation with serum 37 C at different points (0, 24, 48 and 72 h, n=3). (B) Whole-body SPECT images showing the biodistribution of 67Ga-NOTA-SNs compared with free 67Ga during 72 h (n=5).

We finally investigated the possibility of surface-modification of NOTA-SNs without interfering with the radiolabeling procedure, to determine if it is possible to modulate the in vivo behavior.48 Among the different strategies for surface modification that have been reported to date, PEGylation is the most established approach.49 We coated NOTA-SNs with PEG (NOTA-PEG-SNs), using for this purpose a lipid-PEG derivative. However, it is well known that PEGylation might also lead to relevant drawbacks, such as the development of an immunological response, antibody generation and toxic side effects caused by the oxidative side products.50 Bearing in mind these limitations, we have also investigated the in vivo effect of an alternative coating, hyaluronic acid (NOTA-HA-SNs). HA is a biocompatible polysaccharide widely used in biomedical research that has been reported to increase the circulating time of lipid nanoparticles.51,52 Surface-modified nanoemulsions (NOTA-PEG-SNs and NOTA-HA-SNs) presented a similar size than the reference formulation (NOTA-SNs) (Figure 5A). With respect to the zeta potential, relevant modifications were only noticed in the case of NOTA-HA-SNs, which rendered more negative values (Figure 5B). Radiolabeling with 67Ga was successfully done, leading to RCY of 80 8% and 76 1% for NOTA-HA-SNs and NOTA-PEG-SNs, respectively (Figure 5C), indicating that the coatings do not significantly interfere in the interaction between the chelator and the radioisotope, and that coated NOTA-HA-SNs and NOTA-PEG-SNs could be tracked by SPECT in a comparable fashion to the reference formulation (NOTA-SNs) (Figure S7, Supporting Information).

Figure 5 (A) NOTA-HA-SNs and NOTA-PEG-SNs hydrodynamic size distribution measured by DLS (171 5 nm and 138 8 nm, respectively, results are expressed as mean standard deviation, n=3), (B) Zeta potential of NOTA-HA-SNs and NOTA-PEG-SNs measured by LDA ( 64 2 mV and 50 1 mV respectively, results are expressed as mean standard deviation, n=3). (C) Radiochemical yield of 67Ga-NOTA-HA-SNs and 67Ga-NOTA-PEG-SNs (n=3). (D) Quantitative analysis expressed as heart to liver ratio showing the differences in biodistribution between intravenously injected 67Ga-nanoemulsions.

A dynamic SPECT study was then carried out, and the tracer uptake ratio between heart and liver was calculated to evaluate the circulation/elimination pharmacokinetic profile. As shown in Figures 5E, 67Ga-PEG-NOTA-SNs showed significantly higher circulation in the bloodstream in line with previous reports referring to PEGylated nanoemulsions.53 Noteworthy, the PEGylation effect is observed even at a very low density (3 mol%), in concordance to other reports of nanoemulsions in which PEG densities vary between 0.5 and 50 mol% with respect to the total amount of surfactant.53,54 In the case of NOTA-HA-SNs, the results were comparable to the reference formulation of NOTA-SNs, a fact that could be explained by the influence of the HA molecular weight and density of the coating. These factors will therefore need further optimization and will be the subject of future work intended for the development of applications in cancer nanotheranostics where HA coating could be particularly relevant to improve accumulation in the tumor.55,56 Altogether, these results confirm that it is possible to modulate the composition and in vivo behavior of NOTA-SNs, to open up their application in specific indications in the biomedical field.

We described here a simple and highly efficient preparation method for chelator-functionalized biocompatible SNs and the subsequent radiolabeling with 68Ga and 67Ga. The radiolabeled formulations showed great radiochemical properties for in vivo applications and were efficiently followed-up by PET and SPECT imaging. Importantly, we have also proved that the biodistribution of the SNs can be modulated by modifying the surface properties. The capacity to modulate the radiolabeling, modality of imaging and tracking period, as well as the biodistribution properties, highlight the interest of SNs, which have the potential to be easily adapted to the requirements of different and specific biomedical applications. In summary, we believe that SNs have the potential for the development of advanced probes for nuclear imaging and nanotheranostics. In particular, future experiments could involve the evaluation of 68/67Ga-SNs in tumor bearing animal models to further determine the real potential of this formulation in cancer nanotheranostics, taking into account the anticancer properties of 67Ga.

All data generated or analyzed during this study are included in this published article and its Supporting Information file.

Animal experiments were conducted according to the ethical and animal welfare committee at CNIC and the Spanish and EU legislation. Experimental protocols were approved by Madrid regional government (PROEX16/277).

All authors contributed to data analysis, drafting or revising the article, have agreed on the journal to which the article will be submitted, gave final approval for the version to be published, and agreed to be accountable for all aspects of the work.

Authors thank the financial support given by Instituto de Salud Carlos III (ISCIII) and European Regional Development Fund (FEDER) (PI15/00828, PI18/00176 and DTS18/00133), by ERA-NET EURONANOMED III project METASTARG (AC18/00045) and by Asociacin Espaola Contra el Cncer (AECC, IDEAS18153DELA). The first author also acknowledges the financial support from Axencia Galega de Innovacin (GAIN) and Xunta de Galicia (IN848C_20170721_7) and ISCII (FI19/00206).

The author reports no conflicts of interest in this work.

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Biodistribution of sphingolipid nanoemulsions with 68Ga | IJN - Dove Medical Press

COLUMBUS, Ohio, July 20, 2021 /PRNewswire/ --Matrix Meats, Inc., the leading developer of nanofiber scaffolds manufactured to support the production of clean cultivated meat products,is entering a new phase of growth with the addition of five new team members. The hiring surge marks an important milestone for Matrix Meats, which achieved record success in its oversubscribed seed stage round late last year.

The new employees are spread across various company divisions, but each play a critical role in advancing Matrix Meats' innovative manufacturing and strategic partnership goals.

Devan Ohst is heading Matrix Meats' laboratory as the new Director of Research and Development. Transitioning from his background in regenerative medicine and medical devices, he boasts an impressive rsum, with over eight years in advanced material engineering. Ohst will oversee Matrix Meats' technical operations, research activity, and act as a liaison for the company's partners.

Matrix Meats also welcomed Nichole Brown as the company's inaugural Director of Operations. Brown will be spearheading the company's growth strategy and structure as the cultivated meat sector continues to soar. Following 12 years in food and restaurant management, Brown has worked with both international franchises, such as Taco Bell, as well as burgeoning startups. She is a crucial component to furthering Matrix Meats' leadership in groundbreaking, ethical meat production, which is already solidified by 14 active development partnerships with cultivated meat producers in seven countries.

Kevin Doand Mitch Kahn join Matrix Meats as Project Engineers. Do brings a precise eye for production to the company, using his passion for sustainability and climate change to scale up Matrix Meats' scaffolding development. He was an obvious choice for Matrix Meats following his five-month internship under the company's Director of Research and Development, Devan Ohst. Bringing six years of hands-on medical and laboratory experience to Matrix Meats, Kahn harnesses his background in biomedical engineering to put nanofiber scaffolds through intensive, iterative processes. His expertise in materials science and polymer replacement have equipped him with the skills to assess viable candidates for scaffold creation.

Hardy Castada, PhDwas inspired by the burgeoning plant-based meat movement when he joined Matrix Meats as a Senior Food Scientist. Castada will be utilizing his experience in food science and chemistry to facilitate high quality, safety, and nutrition standards. In his previous role at the Ohio State University Department of Food Science and Technology, Castada spearheaded several innovative food and biomedical projects that were widely published in peer-reviewed journals.

"As with any startup, Matrix Meats has been operating with a lean team since our launch in 2019. We were overwhelmed by the fervent interest and positive attention received during last year's seed stage round, and it gave us the confidence to grow our team and support our position in cultivated meat production," said Matrix Meats CEO Eric Jenkusky. "In the short time they've been on board, Devan, Nichole, Kevin, Mitch and Hardy have already been tremendous assets to the company and ardent believers in the global impact of cellular agriculture."

In conjunction with Matrix Meat's numerous team additions, the company also promoted Zac Graber from Operations Manager to Director of Business Development. Graber has been with Matrix Meats since the beginning of 2020, becoming the third employee to join the rapidly growing startup.

Matrix Meats completed its seed stage round in December of 2020 and achieved oversubscribed investment from companies such as Unovis Asset Management, CPT Capital, Siddhi Capital and Clear Current Capital.

About Matrix Meats, Inc.

Matrix Meats, Inc., based in Columbus, Ohio, is a designer and manufacturer of the foremost nano-fiber scaffolds to enable the production of clean, healthy, and environmentally friendly cultured meat to ethically feed the world. Further information: http://www.matrixmeats.com

Press ContactErin MandzikJConnelly862-246-9911[emailprotected]

SOURCE Matrix Meats

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Matrix Meats Adds to Team as Interest in Cultivated Meat Grows - PRNewswire

Global Nanomedicine in Central Nervous System Injury and Repair Market, By Product (Therapeutics, Regenerative Medicine, In-Vitro Diagnostics, In-Vivo Diagnostics, Vaccines), Application (Clinical Oncology, Infectious Diseases, Clinical Cardiology, Orthopedics, Others), Country (U.S., Canada, Mexico, Germany, Italy, U.K., France, Spain, Netherlands, Belgium, Switzerland, Turkey, Russia, Rest of Europe, Japan, China, India, South Korea, Australia, Singapore, Malaysia, Thailand, Indonesia, Philippines, Rest of Asia- Pacific, Brazil, Argentina, Rest of South America, South Africa, Saudi Arabia, UAE, Egypt, Israel, Rest of Middle East & Africa) Industry Trends and Forecast to 2028.

The nanomedicine in central nervous system injury and repair market is expected to gain market growth in the forecast period of 2021 to 2028. Data Bridge Market Research analyses the market to reach at an estimated value of USD 51,419.82 million by 2028 and grow at a CAGR of 9.91% in the above-mentioned forecast period. Increase in the prevalence of central nervous system diseases such as Parkinsons disease, senile dementia, Alzheimer disease, ocular diseases among others drives the nanomedicine in central nervous system injury and repair market.

Download Exclusive Sample Report (350 Pages PDF with All Related Graphs & Charts) @ https://www.databridgemarketresearch.com/request-a-sample/?dbmr=global-nanomedicine-in-central-nervous-system-injury-and-repair-market

Major Players:-

The major players covered in the nanomedicine in central nervous system injury and repair market report are Abbott, Ablynx N.V, California Life Sciences Association, CELGENE CORPORATION, Teva Pharmaceutical Industries Limited, GENERAL ELECTRIC COMPANY, Merck Sharp & Dohme Corp (a subsidiary of Merck & Co., Inc), Pfizer Inc, Nanosphere Inc, Johnson & Johnson Private Limited and BD among other domestic and global players.

Competitive Landscape and Nanomedicine in Central Nervous System Injury and Repair Market Share Analysis

The nanomedicine in central nervous system injury and repair market competitive landscape provides details by competitor. Details included are company overview, company financials, revenue generated, market potential, investment in research and development, new market initiatives, global presence, production sites and facilities, production capacities, company strengths and weaknesses, product launch, product width and breadth, application dominance. The above data points provided are only related to the companies focus related to nanomedicine in central nervous system injury and repair market.

Nanomedicine is defined as the nanotechnology which is used for treating, diagnosing, preventing diseases and traumatic injury, and to control of human biological systems using engineered nanodevices and nanostructures at the molecular level. Nanomedicine uses nano-tools that are 1000 times smaller than a cell for treatment of single cell and is also used in polymer therapeutics, regenerative medicine and targeted drug delivery.

Rise in the awareness related to nanomedicine applications is the vital factor escalating the market growth, also rise in thegovernmentfocus in terms of high funding for life science research and technological advancements in manufacturing process of nanomedicine, increase in the use of nanomedicine as probe or contrast agent in medical imaging techniques to extend the application of imaging and to improve the quality of images and rise in the healthcare expenditures are the major factors among others driving the nanomedicine in central nervous system injury and repair market. Moreover, rise in the technological advancements and modernization in the healthcare devices and rise in the risingresearch and developmentactivities in the healthcare sector will further create new opportunities for nanomedicine in central nervous system injury and repair market in the forecasted period of 2021-2028.

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However, high cost associated with nanomedicine based devices, rise in the stringent government regulations and increase in the risk of environment contamination due to release of toxic nanomaterials are the major factors among others which will obstruct the market growth, and will further challenge the growth of nanomedicine in central nervous system injury and repair market in the forecast period mentioned above.

This nanomedicine in central nervous system injury and repair market report provides details of new recent developments, trade regulations, import export analysis, production analysis, value chain optimization, market share, impact of domestic and localised market players, analyses opportunities in terms of emerging revenue pockets, changes in market regulations, strategic market growth analysis, market size, category market growths, application niches and dominance, product approvals, product launches, geographic expansions, technological innovations in the market. To gain more info on the nanomedicine in central nervous system injury and repair market contact Data Bridge Market Research for an Analyst Brief, our team will help you take an informed market decision to achieve market growth.

Nanomedicine in Central Nervous System Injury and Repair Market Scope and Market Size

The nanomedicine in central nervous system injury and repair market is segmented on the basis of product and application. The growth amongst these segments will help you analyse meagre growth segments in the industries, and provide the users with valuable market overview and market insights to help them in making strategic decisions for identification of core market applications.

The nanomedicine in central nervous system injury and repair market is also segmented on the basis ofapplicationinto clinical oncology, infectious diseases, clinical cardiology, orthopedics and others.

Nanomedicine in Central Nervous System Injury and Repair Market Country Level Analysis

The nanomedicine in central nervous system injury and repair market is analysed and market size insights and trends are provided by product and application as referenced above.

The countries covered in the nanomedicine in central nervous system injury and repair market report are U.S., Canada and Mexico in North America, Germany, France, U.K., Netherlands, Switzerland, Belgium, Russia, Italy, Spain, Turkey, Rest of Europe in Europe, China, Japan, India, South Korea, Singapore, Malaysia, Australia, Thailand, Indonesia, Philippines, Rest of Asia-Pacific (APAC) in the Asia-Pacific (APAC), Saudi Arabia, U.A.E, South Africa, Egypt, Israel, Rest of Middle East and Africa (MEA) as a part of Middle East and Africa (MEA), Brazil, Argentina and Rest of South America as part of South America.

North America dominates the nanomedicine in central nervous system injury and repair market due to rise in the presence of technologically advanced healthcare infrastructure in this region. Asia-Pacific is the expected region in terms of growth in nanomedicine in central nervous system injury and repair market due to rise in the awareness about nanomedicine and high prevalence of chronic diseases in countries in the region.

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The country section of the nanomedicine in central nervous system injury and repair market report also provides individual market impacting factors and changes in regulation in the market domestically that impacts the current and future trends of the market. Data points such as consumption volumes, production sites and volumes, import export analysis, price trend analysis, cost of raw materials, down-stream and upstream value chain analysis are some of the major pointers used to forecast the market scenario for individual countries. Also, presence and availability of global brands and their challenges faced due to large or scarce competition from local and domestic brands, impact of domestic tariffs and trade routes are considered while providing forecast analysis of the country data.

Healthcare Infrastructure growth Installed base and New Technology Penetration

The nanomedicine in central nervous system injury and repair market also provides you with detailed market analysis for every country growth in healthcare expenditure for capital equipments, installed base of different kind of products for nanomedicine in central nervous system injury and repair market, impact of technology using life line curves and changes in healthcare regulatory scenarios and their impact on the nanomedicine in central nervous system injury and repair market. The data is available for historic period 2010 to 2019.

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Customization Available: Global Nanomedicine in Central Nervous System Injury and Repair Market

Data Bridge Market Researchis a leader in advanced formative research. We take pride in servicing our existing and new customers with data and analysis that match and suits their goal. The report can be customised to include price trend analysis of target brands understanding the market for additional countries (ask for the list of countries), clinical trial results data, literature review, refurbished market and product base analysis. Market analysis of target competitors can be analysed from technology-based analysis to market portfolio strategies. We can add as many competitors that you require data about in the format and data style you are looking for. Our team of analysts can also provide you data in crude raw excel files pivot tables (Factbook) or can assist you in creating presentations from the data sets available in the report.

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Nanomedicine in Central Nervous System Injury and Repair Market Report- Trends Key Programs Analysis and Competitive Landscape Analysis The Manomet...

COVID-19s outbreak has coincided with investments flooding into nanomedicine healthcare companies. The World Nano Foundation and Nano Magazine have highlighted a report by marketdataforecast.com that the global nanomedicine market, worth $141.34 billion in 2020, will rise to $258.11bn by 2025.

The report also highlights a huge upsurge of investment support from governments and funds to develop nano therapies for vaccines, diagnostic imaging, regenerative medicine, and drug delivery following the impact of COVID-19.

Furthermore, nanomedicine offers huge advantages for wider healthcare also impacted by the pandemic and Long-COVID after-effects upon cardiovascular, respiratory, neurological, immunological-related diseases.

This aligns with investment monitoring platform Pitchbooks forecast that health tech investment overall will top $10 trillion by 2022 and that nanomedicine investment has grown the sector by 250% in the last five years.

Median nanotech healthcare companies' deal sizes have also doubled since 2019, from 1 million to 2m in the last 12 months, while the number of deals in 2020 was greater than ever, overtaking 100 deals in a single year for the first time.

Investment is already aiding innovation as nanotech researchers and scientists work to improve biomedical devices such as prosthetics, provide new cancer treatments, and develop bone healing therapies, along with more innovations that could transform global healthcare.

Nanotech researchers have found nanobodies that block the COVID-19 and, potentially, other coronaviruses from entering cells and developed mask designs at nanoscale making them both cheaper and more effective.

The fast global response to the pandemic was also enabled by nanotechnology, being pivotal in Pfizer and AstraZeneca vaccine development and Innova Medical Groups 30-minute lateral flow COVID tests.

World Nano Foundation co-founder Paul Stannard said COVID-19 highlighted weaknesses in healthcare systems across the developed world, proving that long-term, innovative solutions are needed to enable change and prevent future pandemics, with nanomedicine playing an ever greater role in this transformation of global healthcare.

And while impressed by rising investments in and recognition for the nanotech sector, he warned against any let-up in this trend:

Nanotechnology is not only crucial to our current healthcare systems, but researchers and scientists in this field are on the cusp of therapies, devices, and innovation that will revolutionize how we move forward.

To ensure pandemic preparedness, high-quality healthcare, and longevity, we must invest in nano healthtech and care innovations.

His message was echoed by Kojo Annan (son of late and former UN secretary-general Kofi Annan) who is a general partner in the Luxembourg-based Vector Innovation Fund, which recently launched a sub-fund raising an initial $300m for pandemic protection and preparedness.

Annan said: A virtuous circle is developing between investment and healthtech.

Lately, we have seen the development of multiple vaccines, acceleration of technologies linked to decoding the genome, the rise of nanomedicine and the use of artificial intelligence to monitor infectious diseases and new pathogens.

More investment in sustainable healthtech funding can only accelerate this trend, bringing fairer and global distribution of healthcare, greater affordability, and preventive and early intervention healthcare, all ultimately improving the longevity of life.

The pandemic has also transformed telemedicine investment and demonstrated that nonsense and innovation could deliver more resilient societies and ecosystems for healthcare.

Written by Steve Philp of The World Nano Foundation.

Korea IT Times

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Nanomedicine is transforming healthcare innovation - Korea IT Times

Image Credit:Giovanni Cancemi/Shutterstock.com

Traditional cancer therapies pose the risk of causing damage to healthy tissue as they work to eradicate cancer cells. Scientists are currently working on therapeutics based on nanotechnology to overcome this limitation and increase survival probabilities in several types of cancer.

Nanotechnology enhances chemotherapy and reduces its adverse effects by guiding drugs to selectively target cancer cells. It also guides the surgical resection of tumors with higher levels of accuracy and enhances the efficacy of radiotherapies and other current treatment options. The result is decreased risk to the patient and enhanced survival probabilities.

Researchers are developing novel therapeutics with newly discovered nanoparticles that have novel properties to be leveraged in medical science. While tiny in size, nanoparticles encapsulate small pharmaceutical compounds. The relatively large surface area of nanoparticles allows them to be decorated with ligands, strands of DNA and RNA, peptides, or antibodies. These add-ons give the nanoparticle additional functionality that enhances the therapeutic effect or helps direct a nanoparticle to a specific location. As a result, nanoparticles facilitate combination drug delivery, multi-modality treatment, and theranostic, action (combined therapeutic and diagnostic). The energy absorption and re-radiation properties of nanoparticles also allows them to improve laser ablation and hyperthermia applications, which disrupt diseased tissue.

Nanoparticle research in oncology is currently progressing rapidly, with several major lines of enquiry emerging such as the development of nanoparticle packages, active pharmaceutical ingredients to facilitate the exploration of a broader range of active ingredients, and the establishment of immunogenic cargo and surface coatings as adjuvants to nanoparticle-mediated therapy, radio- and chemotherapy, and stand-alone therapies.

Below, we discuss the major applications of nanotechnology in oncology.

The primary use of nanotechnology in oncology is within the delivery of drugs. Much research has shown that nanotechnology has successfully been used to design multiple systems that improve the pharmacokinetics of a pharmaceutical and reduce the related toxicities. These systems limit the adverse events of the drugs and augment a patients survival chances. They also allow chemotherapies to be more selective as they help deliver the drugs to the specific tumor tissues. These methods involve the development of nano-sized carriers that encompass and deliver the drug to its target.

There are numerous examples of these types of systems. One recent methodology has been used to increase the efficacy of chemotherapy drugs used to treat bowel cancer. The results of clinical trials suggested that the nanoparticle delivery system could help increase survival rates of bowel cancer, the third most common cancer in the world, by helping the delivery of chemotherapy drugs directly to the diseased organs. In studies with animals, the system was proven to be effective at delivering Capecitabine (CAP) to the diseased cells while bypassing healthy cells. This reduced toxic side effects and enhanced the efficacy of tumor reduction activity.

Recent research has demonstrated the efficacy of nano-sized carriers in delivering alternative, herbal-based therapeutics. Scientists have created a novel targeted therapy to treat triple-negative breast cancer (TNBC) that utilizes nano-carriers to help deliver gambogic acid (GA), a Chinese medicine compound, to specific targets. Studies have shown that the novel methodology was effective at enhancing the anti-cancer effect of GA and limiting damage to healthy tissue. As a result, the use of GA may emerge as a more effective therapeutic option for the treatment of TNBC.

Another encouraging area of nanotechnology in oncology is its use in enhancing immunotherapy. While immunotherapy has already been established as an exciting and potentially highly effective treatment option for various types of cancer, the proportion of patients who respond positively to immunotherapy remains low, with only around 15% of patients demonstrating an objective response rate across indications. This is linked to the multiple immune-evasion methods of the tumor.

To help boost the immune systems efficacy against cancer, nanotechnology is being leveraged to manage the spatiotemporal control of the immune system. The idea is that naturally, the immune system is spatiotemporally controlled. Therefore, to work effectively, therapies that impact the immune system should also be spatiotemporally controlled. Recent research has demonstrated that nanoparticles and biomaterials allow scientists to control the delivery, pharmacokinetics, and location of immunomodulatory compounds, generating responses that cannot be elevated by administering the same compounds within a solution.

Radiotherapy is administered to around half of cancer patients at some point during their treatment. Radiotherapy is effective at reducing the size of tumors by exposing them to high-energy radiation, however, this radiation can also damage healthy cells. Scientists have been working on enhancing the effect of radiotherapy, as well as developing novel externally applied electromagnetic radiation. As a result, it is possible that the combination of nanotechnology and radiotherapy may produce more effective results than radiotherapy alone.

How nanoparticles could change the way we treat cancer | Joy WolframPlay

Video Credit: TED/YouTube.com

HKBU and Cornell University develop novel targeted therapy for breast cancer with nanotechnology and Chinese medicine. EurekAlert!. Available at: https://www.eurekalert.org/pub_releases/2021-05/hkbu-hac051121.php

Goldberg, M., 2019. Improving cancer immunotherapy through nanotechnology. Nature Reviews Cancer, 19(10), pp.587-602. https://www.nature.com/articles/s41568-019-0186-9

Targeting Bowel Cancer with Nanotechnology. GEN. Available at: https://www.genengnews.com/topics/targeting-bowel-cancer-with-nanotechnology/

van der Meel, R., Sulheim, E., Shi, Y., Kiessling, F., Mulder, W. and Lammers, T., 2019. Smart cancer nanomedicine. Nature Nanotechnology, 14(11), pp.1007-1017. https://www.nature.com/articles/s41565-019-0567-y

Disclaimer: The views expressed here are those of the author expressed in their private capacity and do not necessarily represent the views of AZoM.com Limited T/A AZoNetwork the owner and operator of this website. This disclaimer forms part of the Terms and conditions of use of this website.

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The Future of Cancer Treatment Using Nanotechnology - AZoNano

Petri, who serves as Wade Hampton Frost Professor of Medicine and is stepping down as chief of the Division of Infectious Diseases and International Health at UVA, has worked at the University continuously for more than 30 years as a physician, scientist and educator. Last year, he shifted his work to pursue understanding of the coronavirus SARS-CoV-2. He became a trusted voice of reason and comfort to the UVA community extending his knowledge to the nation via online media during the stressful time of the pandemic.

No discussion of Bill would be complete without mentioning what he has done over the last year-plus, during the pandemic, Executive Vice President and Provost Liz Magill said, in presenting the award to him. I can say Jim [Ryan] and I are grateful for his constant availability, tenacity and servant leadership throughout this dark time.

Petri isnt just good at explaining science. Hes also been at the forefront of research, leading a multi-center team effort. He has applied his expertise in vaccine development to produce a mucosally administered, nano-formulated vaccine against the virus responsible for the COVID-19 illness. In addition to his design of the vaccine technology, he is also a most adept and capable team scientist, leading a multicenter effort in this timely, important work, as the citation notes.

Among his responses to this pandemic, he has cared for multiple patients infected with COVID-19, and along the way, educated numerous medical students and young physicians on its medical management.

An expert in infectious diseases, he has focused on several gastrointestinal illnesses and their impact on peoples health and lives, particularly children. Magill pointed out that he is world-renowned for this research, adding, None other than Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases at the NIH and himself a household name, said, Petri is the worlds premier investigator on diarrhea as well as a consummate physician-scientist, training program director, and institutional leader.

Magill said, His research and publications on understanding and treating these diseases have had life-changing impact for millions of patients the world over.

At UVA, he earned his medical degree and a Ph.D. in microbiology, as well as fellowship training in infectious diseases in the School of Medicine, before returning to join the faculty.

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Thomas Jefferson Awards Highlight Research and Service to the University - UVA Today

Global Nanobots Market Report Provides Detailed Study Of Industry Players, Business Strategies, Latest Developmental Trends, And Market Growth Rate

The globalNanobots marketreport offers a thorough study of the market in the estimated period. The important players Xidex Corp, Zymergen Inc, Synthace Limited, Ginkgo Bioworks, Advanced Diamond Technologies, Advanced Nano Products Co Limitedin the global Nanobots market are mentioned along with their strong points as well as weak points in this report. It covers almost all aspects of the global Nanobots market including challenges, demand, drivers, and opportunities. The report reviews the impact of these aspects on every market region as well. The value chain analysis and vendor list are also included in the global Nanobots market report.

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The global Nanobots market is studied in terms of technology, topography, and consumers. The report also covers the market volume during the estimated period. The distinctiveness of the global Nanobots market research report is the representation of the Nanobots market at both the global and regional level.

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Global Nanobots Market 2020 | Research Report Covers | (COVID-19 Analysis) | Industry Research, Drivers, Top Trends | Global Analysis And Forecast to...

NEVE ILAN, Israel, Oct. 29, 2020 (GLOBE NEWSWIRE) -- NANO-X IMAGING LTD (https://www.nanox.vision/) (Nanox or the Company), an innovative medical imaging company, announced today it has signed an agreement with Ambra Health, a leading medical data and image management cloud software company, to facilitate the transfer of medical images between U.S. hospitals and medical imaging providers.

Per the terms of the agreement, Ambra will serve as the enterprise image exchange solution, integrated with planned U.S. Nanox.ARC system deployments via the Nanox.CLOUD infrastructure, subject to approval of the Nanox.ARC system by the FDA.

The Ambra suite consolidates multiple imaging systems with one flexible, customizable, and low maintenance cloud storage platform that lets medical imaging be accessed securely, anytime, anywhere. Leading facilities use Ambra to connect directly to multiple modalities and imaging systems, creating a unified source of imaging data that is accessible to providers and patients. The unification of imaging data allows for significant daily workflow improvements, opportunities for new research and development, and enhanced communication with patients in image-enabled patient and second opinion portals.

Ambra's network allows providers to seamlessly connect with innovative imaging partners like Nanox. Ambra has over eight billion images under its management and is used in over 50 countries.

"It is our intent to provide seamless image exchange once our systems are approved by the FDA and we commence deployments. By working with Ambra, we can directly connect our modalities at hospitals with imaging providers with minimal integration effort and a high level of data-privacy, said Ran Poliakine, Founder and CEO of Nanox.

Digital health companies like Ambra Health and Nanox are on a mission to streamline the image management process so that critical medical imaging data is available when and where providers need it, said Andrew Duckworth, VP of Business Development at Ambra Health.

About Nanox:Nanox, founded by the serial entrepreneur Ran Poliakine, is an Israeli corporation that is developing a commercial-grade digital X-ray source designed to be used in real-world medical imaging applications. Nanox believes that its novel technology could significantly reduce the costs of medical imaging systems and plans to seek collaborations with world-leading healthcare organizations and companies to provide affordable, early detection imaging service for all. For more information, please visit http://www.nanox.visio

About Ambra HealthAmbra Health is a medical data and image management SaaS company. Intuitive, flexible, scalable and highly interoperable, the Ambra cloud platform is designed to serve as the backbone of imaging innovation and progress for healthcare providers. It empowers some of the largest health systems such as Memorial Hermann, Johns Hopkins Medicine, UC San Diego and New York Presbyterian, as well as radiology practices, subspecialty practices, and life sciences organizations to dramatically improve imaging and collaborative care workflows. As expert partners, we listen to our customers, understand their needs, and apply our extensive knowledge to deliver innovative medical image management solutions for the future of healthcare, now. Discover what the Ambra medical imaging cloud can do for you at http://www.ambrahealth.com.

Forward Looking StatementThis press release may contain forward-looking statements that are subject to risks and uncertainties. All statements that are not historical facts contained in this press release are forward-looking statements. Such statements include, but are not limited to, any statements relating to the initiation, timing, progress and results of Nanox's research and development, manufacturing and commercialization activities with respect to its X-ray source technology and the Nanox.ARC. In some cases, you can identify forward-looking statements by terminology such as can, might, believe, may, estimate, continue, anticipate, intend, should, plan, should, could, expect, predict, potential, or the negative of these terms or other similar expressions. Forward-looking statements are based on information Nanox has when those statements are made or management's good faith belief as of that time with respect to future events, and are subject to risks and uncertainties that could cause actual performance or results to differ materially from those expressed in or suggested by the forward-looking statements. Factors that could cause actual results to differ materially from those currently anticipated include: risks related to business interruptions resulting from the COVID-19 pandemic or similar public health crises could cause a disruption of the development, deployment or regulatory clearance of the Nanox System and adversely impact our business; Nanox's ability to successfully demonstrate the feasibility of its technology for commercial applications; Nanox's expectations regarding the necessity of, timing of filing for, and receipt and maintenance of, regulatory clearances or approvals regarding its X-ray source technology and the Nanox.ARC from regulatory agencies worldwide and its ongoing compliance with applicable quality standards and regulatory requirements; Nanox's ability to enter into and maintain commercially reasonable arrangements with third-party manufacturers and suppliers to manufacture the Nanox.ARC; the market acceptance of the Nanox.ARC and the proposed pay-per-scan business model; Nanox's expectations regarding collaborations with third-parties and their potential benefits; and Nanox's ability to conduct business globally, among others. Except as required by law, Nanox undertakes no obligation to update publicly any forward-looking statements after the date of this press release to conform these statements to actual results or to changes in Nanox's expectations.

Media Contacts:

NanoxAlona Steinalona@reblonde.com

Ambra Healthpress@ambrahealth.com888-587-2280

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Nanox Signs With Ambra Health to Enable Image Access and Transfer with US Hospitals and Medical imaging Providers - BioSpace

Global Nano Therapy Marketwas valued US$ XX Mn in 2019 and is expected to reach US$ XX Mn by 2027, at a CAGR of 8.6% during a forecast period.

Market Dynamics

Nanotechnology is the manipulation of matter on an atomic, molecular, and supramolecular scale. Nanotherapy is a branch of Nano medicine that includes using nanoparticles to deliver a drug to a given target location in the body so as to treat the disease through a process called as targeting.

This report provides insights into the factors that are driving and restraining the global Nano Therapy market. Nanotherapy is also referred to as targeted therapy, which offers to transport the molecules to the affected cells to treat the disease without affecting other negative effects on the healthy cells. Nanoparticles allow for multiple functional groups to be added to the surface. Each of the functional groups contributes to the effectiveness of this method of therapy and deliver its components in a controlled way once it gets to the target cells/tissue. Nano therapy is considered as recent technology for some diseases, which are implemented with the help of submicron-sized molecular devices or nanoparticles. Nanoparticles can improve the drug accessibility in the body with strength, drag out the medication, and can upsurge the half-life of plasma and boost the drug specificity. These are the factors driving the growth of the Nano therapy market.

As compared to the conventional methods, this method has increased more popularity owing to its high accuracy when it comes to administering therapeutic formulations. The market is thriving, with around 250 Nano-medical products being verified or used for humans. Though, with Nano therapy, the carrier is protected from degradations, which allows it to reach given target cells in the body for a local reaction. Nano therapy is considerably used in the treatment of diseases like cancer, diabetes, and cardiovascular diseases. A recent study by the Journal of Diabetes and Metabolic diseases has stated that the incidence of MS ranged from 30.5 to 31.5% in China and 35.8 to 45.3% in India.

However, an absence of controlling standards in the examination of Nano therapy and high expenditure of treatment are several of the major factors that are restraining the growth of the Nano therapy market during the forecast period.

The report study has analyzed revenue impact of covid-19 pandemic on the sales revenue of market leaders, market followers and disrupters in the report and same is reflected in our analysis.

Global Nano Therapy Market Segment analysis

Based on Type, the Nanomaterial segment is anticipated to grow at a CAGR of 20.8% during the forecast period. The nanomaterial is the materials with at least one exterior dimension in the size range of nearly 1 to 100 nanometers. The nanomaterial is intended for developing novel characteristics and has the potential to improve quality of life. The nanomaterial is generally used in cosmetics, healthcare, electronics, and other areas currently. Unceasing development and innovation in the field are impelling the growth of the global nanomaterials market. The amazing chemical and physical properties of materials at the nanometer scale allow novel applications. For instance, energy conservation and structural strength improvement to antimicrobial properties and self-cleaning surfaces. Nanotechnology is being increasingly efficient by spending mainly on R&D activities which are resulting in the development of current technologies and innovations with reference to the new materials.

Global Nano Therapy Market Regional analysis

North America region dominated the Nano therapy market with US$ XX Mn in 2019. The availability of technology, increasing healthcare spending, and government funding for research and development are some of the factors boosting the growth of the Nano therapy market in the region. Europe is expected to follow the Americas and bring in the second leading market share for Nano therapy throughout the forecast period. Europe is mainly driven by awareness and improvement in the nanotechnology sector.

Recent Developments

In 08 May 2019- Cisplatin cis-(diammine) dichloridoplatinum (II) (CDDP) is the first platinum based complex approved by the food and drug administration (FDA) of the United States (US). Cisplatin is the first line chemotherapeutic agent used alone or combined with radiations or other anti-cancer agents for a broad range of cancers such as lung, head and neck.

In May 2019- A new study conducted by scientists from the Indian Institute of Technology, Bombay, have designed hybrid nanoparticles to treat cancer. These nanoparticles are made from gold and lipids. These nanoparticles respond to light and can be directed inside the body to release drugs to a targeted area, and are biocompatible, meaning theyre not toxic to a human body.

In September 2019, researchers at Finlands University of Helsinki, in partnership with the bo Akademi University and Chinas Huazhong University of Science and Technology developed an anti-cancer nanomedicine useful for targeted cancer chemotherapy.

The objective of the report is to present a comprehensive analysis of the Global Nano Therapy Market including all the stakeholders of the industry. The past and current status of the industry with forecasted market size and trends are presented in the report with the analysis of complicated data in simple language. The report covers all the aspects of the industry with a dedicated study of key players that includes market leaders, followers and new entrants. PORTER, SVOR, PESTEL analysis with the potential impact of micro-economic factors of the market have been presented in the report. External as well as internal factors that are supposed to affect the business positively or negatively have been analyzed, which will give a clear futuristic view of the industry to the decision-makers.The report also helps in understanding Global Nano Therapy Market dynamics, structure by analyzing the market segments and project the Global Nano Therapy Market size. Clear representation of competitive analysis of key players by Application, price, financial position, Product portfolio, growth strategies, and regional presence in the Global Nano Therapy Market make the report investors guide.Scope of the Global Nano Therapy Market

Global Nano Therapy Market, By Type

Nanomaterial and Biological Device Nano Electronic Biosensor Molecular Nanotechnology Implantable Cardioverter-DefibrillatorsGlobal Nano Therapy Market, By Application

Cardiovascular Disease Cancer Therapy Diabetes Treatment Rheumatoid ArthritisGlobal Nano Therapy Market, By Regions

North America Europe Asia-Pacific South America Middle East and Africa (MEA)Key Players operating the Global Nano Therapy Market

Selecta Biosciences Inc. Cristal Therapeutics Sirnaomics Inc. Nanobiotix Luna CytImmune Science Inc. NanoBio Corporation Nanospectra Biosciences Inc. Nanoprobes Inc. NanoBioMagnetics.n.nu Smith and Nephew NanoMedia Solutions Inc. Nanosphere Inc. DIM Parvus Therapeutics Tarveda Therapeutics

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Global Nano Therapy Market- Industry Analysis and Forecast (2020-2027) - Stock Market Vista

Nanoscience has made an impact on a range of industries. With continuous developments, it will only get more exciting for investors.

Through nanotechnology, nanoscience has undeniably impacteda range of industries, from energy to medicine. In the face of continuous nanotechnology research and development, experts are promising an exciting future for the industry.

The terms nanoscience and nanotechnology have been around for a long time, and its common for them to be used interchangeably. However, its important to note that they are not the same.

According toErasmus Mundus, the European Unions higher education program, nanoscience refers to the study, manipulation and engineering of particles and structures on a nanometer scale. For its part, nanotechnology is described as the design and application of nanoscience.

In simple terms, nanoscience is the study of nanomaterials and properties, while nanotechnology is using these materials and properties to create a new product.

Here the Investing News Network provides a comprehensive look at nanoscience investing and nanomaterials, with an overview of the subjects and where they are headed in the future.

The University of Sydneys Nano Institute describes nanoscience as the study of the structure and function of materials on the nanometer scale.

Nanometers are classified as particles that are roughly the size of about 10 atoms in a row. Under those conditions, light and matter behave in a different way as compared to normal sizes.

These behaviours often defy the classical laws of physics and chemistry and can only be understood using the laws of quantum mechanics, the universitys research page states.

The Institute of Nanoscience of Aragon identifies carbon nanotubes (CNTs) as one example of a component that is designed at the nanoscale level. These structures are stronger than steel at the macroscale level. CNT powders are currently used in diverse commercial products, from rechargeable batteries to automotive parts to water filters.

Scientists, researchers and industry experts are enthusiastic about nanoscience and nanoparticles.

As noted in a study published by Jeffrey C. Grossman, a University of California student, quantum properties come into play at the nanoscale level. In simple terms, at the nanoscale level, a materials optical properties, such as color, can be controlled.

Further, the paper states that the surface-to-volume ratio increases at the nano size, opening up new possibilities for applications in catalysis, filtering, and new composite materials, to name only a few.

In other words, the opening up of surface area, which adds new possibilities, can have drastic effects on industries such as manufacturing. New applications in catalysis can allow manufacturing to be sped up, while new composite materials can add more dimension to an end product.

Nanoscale developments could also lead to increased resources and could play a role in the energy sector by increasing efficiency.

As the Royal Society putsit, the aim of nanoscience and nanotechnologies is to produce new or enhanced nanoscale materials.

Nanomaterials are formed when materials have their properties changed at the nanoscale level. Nanomaterials involve elements that contain at least one nanoscale structure, but there are several subcategories of nanomaterials based on their shape and size.

According to the Royal Society, nanowires, nanotubes and nanoparticles like quantum dots, along with nanocrystalline materials, are said to be nanomaterials.

While these are broader classifications of nanomaterials, each of them has several submaterials. Graphene is one popular submaterial and is an example of a nanoplate.

The Integrated Nano-Science & Commodity Exchange, a self-regulated commodity exchange, includes a wide range of nanomaterials and related commodities and lists more than 1,000 nanomaterials.

The exchange states that its entire product range is in excess of 4,500 products, including CNTs, graphene, graphite, ceramics, drug-delivery nanoparticles, metals, nanowires, micron powders, conductive inks, nano-fertilizers and nano-polymers.

As can be seen, nanoscience and nanotechnology are used in a variety of applications across diverse fields, from energy to manufacturing. The University of Sydneys Nano Institute highlights how nanoscienceimpacts manufacturing, energy and the environment through the continuous development of new nano and quantum materials.

With the advancement of materials science and technology, solutions are being worked on for the health and medicine fields, with nanobots gaining popularity in the medical field.

Similarly, nanomaterials like graphene are having a major impact in the technology field graphene is used for various purposes, including in cooling and in batteries.

According to IndustryARC, the global nanotechnology market is projected to reach US$121.8 billion by 2025, growing at a compound annual growth rate of 14.3 percent between 2020 and 2025.

In the US, the National Nanotechnology Initiative, a US government research and development initiative that involves 20 federal and independent agencies, has received cumulative funding of US$27 billion since 2001 to advance research and development of nanoscale projects.

With growth predicted across multiple areas and industries, and with researchers and institutes working on developing the nanoscience field, investors have a slew of nanotechnology stocks to consider.

One popular investment avenue is via graphene, with companies in the space including Applied Graphene Materials (LSE:AGM,OTC Pink:APGMF) and Haydale Graphene Industries (LSE:HAYD). Meanwhile, nanotech stock options include firms such as NanoViricides (NYSE:NNVC), Nano Dimension (NASDAQ:NNDM) and Sona Nanotech (CSE:SONA).

This is an updated version of an article first published by the Investing News Network in 2019.

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Securities Disclosure: I, Melissa Pistilli, hold no direct investment interest in any company mentioned in this article.

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What is Nanoscience? | Outlook and How to Invest | INN - Investing News Network