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Taking the previously reported compound BH‐7d as the lead, we designed and synthesized a series of piperidinyl‐substituted [1,2,4]triazolo[1,5‐a]pyrimidines, and their anti‐HIV activities as well as cytotoxicities were evaluated. Several compounds exhibited moderate anti‐HIV (IIIB) potency, among which 2b was the most active one (EC50 = 4.29 μM). Structure–activity relationships derived from the antiretroviral results were analyzed. Additionally, most compounds demonstrated reduced cytotoxicity (CC50 > 200 μM) compared with those of BH‐7d and etravirine. Molecular docking study further revealed the binding conformation of 2b in the binding pocket of HIV‐1 reverse transcriptase. [ABSTRACT FROM AUTHOR]

In this study, we report an industrial‐scale fabrication method of a multifunctional polymer composite as a scaffold material for bone tissue engineering. This study successfully demonstrated the potential of applying industrial polymer processing technologies to produce specially functionalized tissue engineering scaffolds. With the inclusion of a newly synthesized multifunctional additive, silver‐doped‐calcium phosphate (silver‐CaP), the composite material exhibited excellent osteogenic inducibility of human adipose‐derived stem cells (hASC) and satisfactory antibacterial efficacy against Escherichia coli and Staphylococcus aureus. Also, relative to previously reported methods of direct loading silver particles into polymeric materials, our composite exhibited significantly reduced silver associated cytotoxicity. The enhanced biocompatibility could be a significant advantage for materials to be used for regenerative medicine applications where clinical safety is a major consideration. The impact of different silver loading methodologies on hASC' osteogenic differentiation was also studied. Overall, the results of this study indicate a promising alternative approach to produce multifunctional scaffolds at industrial‐scale with higher throughput, lower cost, and enhanced reproducibility. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 900–910, 2019. [ABSTRACT FROM AUTHOR]

Abstract: The unique physicochemical properties of silver nanoparticles offer a large potential for biomedical application, however, the serious biotoxicity restricts their usage. Herein, nanogalvanic couple Ag–Fe@Fe3O4 heterostructures (AFHs) are designed to prevent Ag+ release from the cathodic Ag by sacrificial anodic Fe, which can reduce the cytotoxicity of Ag. AFHs are synthesized with modified galvanic displacement strategy in nonaqueous solution. To eliminate the restriction of lattice mismatch between Fe and Ag, amorphous Fe@Fe3O4 nanoparticles (NPs) are selected as seeds, meanwhile, reductive Fe can reduce Ag precursor directly even at as low as 20 °C without additional reductant. The thickness of the Fe3O4 shell can influence the amorphous properties of AFHs, and a series of Janus‐ and satellite‐like AFHs are synthesized. A “cut‐off thickness” effect is proposed based on the abnormal phenomenon that with the increase of reaction temperature, the diameter of Ag in AFHs decreases. Because of the interphase interaction and the coupling effect of Ag and Fe@Fe3O4, the AFHs exhibit unique optical and magnetic properties. This strategy for synthesis of monodisperse heterostructures can be extended for other metals, such as Au and Cu. [ABSTRACT FROM AUTHOR]

A combined methodology involving gamma and pulse radiolysis, product analysis and toxicity studies has been adopted to comprehend the degradation process of a model hydrophobic azo dye, 1-phenylazo-2-naphthol, emphasizing the role of the surfactant, which is an integral part of textile waste. Two new and important findings are underlined in this article. The first is the direct attestation of the hydrazyl radical-parent adduct, formed in the reaction of the dye with e − aq followed by protonation and subsequent addition to the unreacted dye molecule. This has been confirmed from concentration dependent studies. Secondly, we have clearly shown that in the reaction of hydroxyl radical with the dye in Triton X-100 media, the initially produced TX radicals cause reductive degradation of the dye. Identification and detailed analysis of HPLC and GCMS data reveals that similar products are formed in both the reactions of e − aq and OH radicals. Moreover, the cytotoxicity of 10 −4 mol dm −3 dye was found to be reduced significantly after irradiation. Thus, the present study not only depicts new pathways for the degradation of hydrophobic azo dye, but also demonstrates the role of a surfactant in the entire process. [ABSTRACT FROM AUTHOR]

The protein adsorption onto poly(acrylic acid)- block -polystyrene (PAA 22 - b -PS 144) polymersomes has been investigated with regard to structural features, thermodynamic aspects and biological consequences. The light scattering measurements revealed the formation of protein coronas enveloping the polymeric capsules regardless of the chemical nature of the biomacromolecules. The experiments were conducted by using lysozyme, immunoglobulin G - IgG and bovine serum albumin - BSA as model proteins due to their differences concerning size and residual surface charge at physiological pH. The protein adsorption was further confirmed by isothermal titration calorimetry, and the experimental data suggest that the phenomenon is mainly governed by hydrogen bonding and van der Waals interactions. The pre-existing protein layer via the pre-incubation in protein environments notably attenuates the cytotoxicity of the nanomaterial compared to the pristine counterparts. This approach can possibly be extended to different types of assemblies when intermolecular interactions are able to induce protein adsorption and the development of protein coronas around nanoparticles. Such fairly simple method may be convenient to engineer safer nanomaterials towards a variety of biomedical applications when the nanotoxicity is an issue. Additionally, the strategy can possibly be used to tailor the surface properties of nanoparticles by adsorbing specific proteins for targeting purposes. [Display omitted] • Protein adsorption takes place spontaneously at the surface of PAA- b -PS vesicles. • Weight ratio of adsorbed protein is independent of protein size and chemical nature. • The protein layers notably attenuate the cytotoxicity of the polymeric vesicles. • Protein coronas provide beneficial effects to nanomaterials. • Protein adsorption can be used to tailor the surface properties of nanomaterials. [ABSTRACT FROM AUTHOR]

Abstract: A facile approach for polymer gene carriers was used to construct hyaluronic acid (HA) shielding polyplexes due to the electrostatic interaction. By adding HA to PEI/DNA complexes, the ξ-potential of ternary polyplexes was changed from positive to negative. Spherical particles with diameter about 250nm were observed. Ethidium bromide exclusion assay indicated that the electrostatic complexation was loosened after addition of HA. However, DNA disassembly did not occur. The proper reason was that the intensity of negative charges was not strong enough to release DNA from the complexes in our experiment. The stability of PEI/DNA/HA polyplexes in physiological condition was improved and the cytotoxicity was reduced. Comparing with PEI/DNA polyplexes, the uptake and transfection efficiency of HA shielding polyplexes was lower for HEK293T cells probably due to the reduced adsorptive endocytosis, whereas it was higher for HepG2 cells due to HA receptor mediated endocytosis. This facile approach to constructing HA shielding polyplexes might have great potential application in non-viral gene delivery research and tumor therapy. [Copyright &y& Elsevier]

A series of amyloid- β aggregation inhibitors composed of a molecular recognition element (KLVFF) and an aggregation-disrupting part (having an electrostatic and hydrophilic nature) based on amino acid analogs have been synthesized. A quartz-crystal microbalance (QCM) method was applied and found to be very successful in evaluating the inhibitory activity of the A β aggregation, which was observed when the frequency was increased. The QCM can detect a mass change with differences in frequency that correspond to a 1 Hz frequency decrease per 30 pg mass increase on a 4.9 mm2 electrode. Furthermore, bioassay results showed no toxicity of the inhibitor itself against IMR-32 neuroblastoma cells, and remarkably reduced cytotoxicities of both A β1–40 and A β1–42 were exhibited in the presence of these inhibitors. The KLVFF-(EEX)3 derivative was the most efficient A β aggregation among the inhibitors examined here. [ABSTRACT FROM AUTHOR]

[Display omitted] • Synthesis and characterization of BSA-CBX NPs with 72 % encapsulation efficiency. • Stability of BSA-CBX NPs for at least 3 months at room temperature. • Bi-phasic in vitro drug release; controlled release in non-fickian fashion. • Molecular docking showed non-covalent interactions of BSA-CBX with 93 % stability. • Reduced cytotoxicity of BSA-CBX NPs compared to native drug. Carbenoxolone (CBX) is a semi-synthetic plant derivative with pleiotropic pharmacological properties like anti-microbial and anti-inflammatory activities. Though approved for treatment of gastric ulcers, its use is limited due to adverse effects such as cytotoxicity. Bovine serum albumin (BSA) is a natural, non-toxic protein with high water-solubility and low immunogenicity, and is widely used as a nanocarrier for targeted drug delivery. In the present study, controlled release BSA-CBX nanoparticles (NPs) were synthesized by desolvation method to reduce drug cytotoxicity. These NPs showed desirable physicochemical properties such as particle size (∼240 nm), polydispersity index (0.08), zeta potential (−7.12 mV), drug encapsulation efficiency (72 %), and were stable for at least 3 months at room temperature. The drug was released from the BSA-CBX NPs in a biphasic manner in vitro following non-fickian diffusion. Computational analysis determined that the binding between BSA and CBX occurred through van der Waals forces, hydrophobic interactions, and hydrogen bonds with 93 % steric stability. Further, the cytotoxic assays demonstrated ∼1.8–4.9-fold reduction in cytotoxicity using three human cell lines (A549, MCF-7, and U-87). Subsequently, this novel CBX formulation with BSA as an efficient carrier can potentially be used for diverse biomedical applications. [ABSTRACT FROM AUTHOR]

The unique physicochemical properties of silver nanoparticles offer a large potential for biomedical application, however, the serious biotoxicity restricts their usage. Herein, nanogalvanic couple Ag-Fe@Fe 3 O 4 heterostructures (AFHs) are designed to prevent Ag + release from the cathodic Ag by sacrificial anodic Fe, which can reduce the cytotoxicity of Ag. AFHs are synthesized with modified galvanic displacement strategy in nonaqueous solution. To eliminate the restriction of lattice mismatch between Fe and Ag, amorphous Fe@Fe 3 O 4 nanoparticles (NPs) are selected as seeds, meanwhile, reductive Fe can reduce Ag precursor directly even at as low as 20 °C without additional reductant. The thickness of the Fe 3 O 4 shell can influence the amorphous properties of AFHs, and a series of Janus- and satellite-like AFHs are synthesized. A "cut-off thickness" effect is proposed based on the abnormal phenomenon that with the increase of reaction temperature, the diameter of Ag in AFHs decreases. Because of the interphase interaction and the coupling effect of Ag and Fe@Fe 3 O 4 , the AFHs exhibit unique optical and magnetic properties. This strategy for synthesis of monodisperse heterostructures can be extended for other metals, such as Au and Cu.