Nanomedicine: Nanotechnology, Biology and Medicine …

Atomic force microscopy (AFM) was used here to study chronic myeloid leukemia (CML) stem cells in dormant (quiescent) and proliferating stages. Persistence of residual quiescent CML stem cells (LSCs) that later resume proliferation seems to be a common cause of recurrence or relapse of CML. The collage shows a scheme of the AFM method and the found biophysical difference between these cells in the density of the pericellular layer surrounding cells.

This review gathers important and up-to-date information about variable synthetic methods that lead to attainment of magnetic nanoparticles with different shape and size. Moreover, information summarized within this manuscript determines the basics of sensing principles of magnetic nanoparticles. Furthermore here we report functionalization and modification of magnetic nanoobjects in order to achieve surfaces suitable for selective drug delivery, medical diagnosis and applications. Ultimately, one chapter is especially devoted to alternative green synthesis of nanoparticles.

Siderophores and oligopeptides take advantage of specific microbial active transport systems. Particular types of cell penetrating peptides, carbon nanotubes and terpenoid derivatives enter the cells by direct translocation. Dendrimers and large cell penetrating peptides are internalized by endocytosis. All these compounds conjugated with antimicrobials act as nanocarriers and transport the cargoes across the biomembranes. Once the conjugate is internalized, the active component could reach its intracellular target, either after release from the conjugate or in an intact form.

MPLA-coating of HBsAg nanocapsules (NCs) enhanced the uptake of NCs by neonatal and adult monocyte-derived dendritic cells (moDCs). The TLR4 mediated phagocytosis and the additional stimulation with IFN induced up-regulated expression levels of the co-stimulatory molecules CD80/86, the MHC II molecule, and the secretion of the pro-inflammatory cytokines TNF-, IL-12 and IL-6. Neonatal moDCs pulsed with MPLA-HBsAg-NCs plus IFN possessed the ability to trigger nave T cells towards TH1 immunity. The antigen-specific T cell proliferation was associated with the secretion of TH1 cell-specific IFN release.

A poly(phosphorhydrazone) dendrimer capped with amino-bis(methylene phosphonate) end groups enables the proliferation of human NK cells. This specific outcome results from a complex cross-talk between dendrimer-activated monocytes and autologous NK cells. During this crosstalk, dendrimer-activated monocytes are needed to enable the proliferation of NK cells, but ultimately, the NK cells have to kill autologous monocytes to proliferate. Like the yin and the yang, these cells have contrary but interdependent activities at the same time. This specific amplification of NK cells is also possible starting from peripheral blood of multiple myeloma patients, paving the road for NK cell-based anti-cancer immunotherapies.

The enzyme-responsive peptide drug conjugate specifically delivers the drug to prostate cancer cells. The PSA substrate is cleaved in the tumor interstitial space to release the dipeptide-linked TGX-D1, which enters the cells via overexpressed dipeptide transporters in prostate cancer cells. TGX-D1 is finally released from the dipeptide after cleavage of the ester linker inside the cells to exert its pharmacological effect. The intact peptidedrug conjugate may also enter the cells directly via endocytosis, and the ester bond can be cleaved inside the cells to release the active drug.

Overall properties and applications of synthesized magnetic nanoparticles coated by amphotericin B (red balls) or nystatin (blue balls) or their mixture against Candida cells.

Hydrophobic core protected graft copolymers (HC-PGC) such as MPEG-gPLL acylated with oleic acid, promote the formation of nanoparticles of water-insoluble benzophenone-uracyl non-nucleoside reverse transcriptase inhibitors after the co-lyophilization. These nanoparticles bind to the surface of HIV-1 infected effector cells and result in a high selectivity anti-HIV index because of their low toxicity.

Mice were fed with an MCD diet seven days ahead to develop NAFLD, and were then treated with saline, FNB crude drug or FNB-Nanolipo by gavage and meanwhile continuously fed with the MCD diet for another seven days. Compared to the FNB crude drug, the FNB-Nanolipo significantly enhanced oral absorption of FNB and therefore, significantly cured NAFLD induced by the MCD diet.

Iontophoresis for transcutaneous immunization using ovalbumin (OVA) as a model antigen, liposomes and silver nanoparticles (NPAg): in vitro iontophoresis of the liposomal dispersion containing NPAg improved OVA penetration into the viable epidermis, where antigen presenting cells are located. This increase in OVA skin penetration resulted in a humoral immune response similar to that obtained following a subcutaneous injection of OVA. The cellular immune responses that were obtained after iontophoresis of OVA-liposomes and OVA-liposomes w/o NPAg were more evident than those obtained after subcutaneous injection.

We show that polyethyleneimine/magnetic nanoparticles based delivery vector (PEI/MNP) is suitable for production of miRNA-modified endothelial cells in terms of efficiency and safety. The obtained transfected cells can be guided to the site of interest using a magnetic field and their fate can be noninvasively traced using magnetic resonance imaging. This multifunctional approach for transient cell modification bears particular interest as a basis for clinically relevant cell engineering.

The formation of folate targeted CD nanoparticles encapsulating RelA siRNA leads to specific folate mediated uptake in PSMA+ cells, the specific knockdown of RelA and an increase in the half-life of the siRNA

The improvement of osseointegration will be a great challenge for the design of the future generation of bone implants. The application of specific nanotopographies on the surface of bone implants is a potential strategy to achieve improved quality, without the need for changes of the implant design. In the current paper, nanogrooved topographies that were reproduced into epoxy resin cylinders could significantly increase bone regeneration around the implants in a rat femoral condyle model, compared to rough control surfaces.

Different from traditional idea, we designed and synthesized a highly hydrophobic reduction-sensitive docetxel prodrug with a disulfide bond inserted into the linker between docetaxel and vitamin E, which could self-assemble in water to form self-assembled nanoparticles without the help of surface active substances. Compared with a docetaxel Tween80-containing formulation, the unique nanomedicine had many advantages, including high drug payload, advanced stability, superior reproducibility, low toxicty, prolonged circulation and increased therapeutic efficacy. The highly reproducible self-assembled nanoparticles prepared by simple nanoprecipitation technology are more attractive and effective nanomedicines, and might be a promising nano-drug delivery system for other anticancer drug.

Currently, clinical ultrasonography and serum alpha-fetoprotein have limited specificity and sensitivity for the detection of hepatocellular carcinoma (HCC). In this study, based on Au@Ag NRs nanorods surface-enhanced Raman spectroscopy(SERS), we performed a label-free, non-invasive SERS test on 230 serum samples (47 HCC, 68 breast cancer, 55 lung cancer, and 60 normal control) to identify distinctive Raman spectrum peaks as a metabolic fingerprint to predict HCC. This paper is the first to report on the detection of serum metabolic profiles in HCC patients through SERS. In addition, this study is also the first to detect and compare serum SERS in three types of cancer to determine the general serum metabolic alterations among cancer patients. Furthermore, SERS combined with orthogonal partial least squares discriminant analysis exhibited good diagnostic performance for HCC, with the receiver operating characteristic curve having an area under curve value of 0.991. The present study provides new insights into the detection of metabolic processes related to the biology of HCC through Raman spectroscopy.

Radiotherapy is a key component of prostate cancer treatment. Because of its importance, there has been high interest in developing agents and strategies to further improve the therapeutic efficacy of radiotherapy. In this study, we engineered a nanoparticle formulation of Dbait, a new class of DNA damage repair inhibitor, with H1 (folatepolyethylenimine600cyclodextrin) nanopolymer. We demonstrated that H1/Dbait nanoparticle was a potent radiosensitizer in vitro and in vivo. Our study supports further investigations using nanoparticles to deliver DNA damage repair inhibitors to improve the therapeutic index of radiotherapy for prostate cancer.

Cerium oxide nanoparticles (20mg/kg) given intravenously twice a week prolonged survival in SOD1G93A transgenic mice. Treatment was started at the onset of muscle weakness at ~113days of age.

The hallmark of chronic obstructive lung diseases, such as COPD and CF, is intermittent or stable exacerbation that initiates progression of chronic inflammatory lung disease. Although, we have made significant progress in the development of anti-inflammatory drugs to treat these diseases but in order to provide sustained drug-delivery to target cells, there is a need for nano-carrier(s) that can circumvent obstructive airway defense. Hence, in this study we evaluated the efficacy of neutrophil-targeted nanoparticle in delivering non-steroidal anti-inflammatory drug, ibuprofen to control Pa-LPS induced inflammatory lung disease and cigarette smoke induced emphysema.

Subretinal injection of SP-PA-PRPF31 nanoparticles in heterozygous knock-in (KI) Prpf31A216P/+ mice. The retinal thickness measured by optical coherence tomography (OCT) in KI Prpf31A216P/+ mice treated with SP-PA-PRPF31nanoparticles was a similar value to wild type mice. These nanomedicines not only improved visual function but also retarded or reversed retinal degeneration in KI Prpf31A216P/+ mice, evidenced by the absence of retinal atrophy.

Gold nanorods (GNRs) inhibit respiratory syncytial virus (RSV) in vitro and in vivo. The antiviral gene expression study showed interplay of Toll-like receptor, NOD-like receptor and RIG-I-like receptor signaling pathways. Transmission electron microcopy, histological investigation and cytokine analysis indicate that GNRs stimulates innate immune response resulting in RSV inhibition.

This figure shows the formation of G4AcFaHSTK compact nanoparticles from the interaction between HSTK-based plasmids and partially acetylated, folic acid-conjugated, cationic 4th-generation polyamidoamine dendrimers (G4AcFa). Also, it shows the application of the real-time PFQNM mode of AFM to visualize the morphological and nanomechanical changes of individual live and dividing HeLa cells in their native environment upon their attack by G4AcFaHSTK.

After proper oral immunization schedules using SBA-15 as adjuvant, the recruitment of inflammatory cells to Peyers patches and mesenteric lymph nodes and the enhanced production of specific antibodies, as well as the non-influence of silica in the polarization to TH1 or TH2 immune responses, were shown.

Increased levels of soluble amyloid-beta (A) oligomers are suspected to underlie Alzheimer's disease (AD) pathophysiology through the formation of uncontrolled multi-subunit A pores in cellular membranes. In this study, the efficacy of small molecule NPT-440-1 modulation of A1-42 pore permeability was examined. We show that co-incubation of B103 rat neuronal cells with NPT-440-1 and A1-42 prevented calcium influx. In purified lipid bilayers, preincubation prior to membrane introduction was required to prevent conductance despite the presence of pore structures. The results point to compound-induced structural modulation leading to collapsed pores and suggest that pharmacological modulation of A1-42 could prevent AD pathogenesis.

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