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In this study, we recruited chitosan (CS) both for selenium nanoparticles (SeNPs) synthesis and for the development of a thermoresponsive nanocomposite hydrogel with the addition of glycerol phosphate (GP). Considering that SeNPs are toxic at high concentrations, five different ingredients of the nanocomposite hydrogel system with low concentrations of SeNPs (1.25-20 μg/mL) were prepared. The gelation conditions, structural characteristics, and mechanical properties of SeNPs-loaded thermosensitive CS/GP hydrogels were investigated. We also evaluated their antioxidizing activities and biocompatibility of the CS/GP/SeNPs hydrogels. Our study demonstrated that the incorporation of SeNPs in the hydrogel improved its mechanical properties, antioxidant activity, and degree of swelling. According to the properties of SeNPs and CS/GP thermosensitive hydrogels, the combination of these two technologies in an appropriate manner would be a promising antioxidant system for drug delivery and tissue engineering.

Macrophages have high plasticity and heterogeneity, and can suppress or mediate inflammation, depending on their cytokine secretion and phenotype. Regulating macrophage polarization into its M2 phenotype has a remarkable effect on inflammatory inhibition, inducing the regeneration of injured tissues. Here, we synthesized two heptamannosylated β-cyclodextrin derivatives (CD-Man7 and C3-CD-Man7) and demonstrated that their multivalent mannose ligands could induce M2 macrophage polarization to accelerate wound healing. Unlike hydrophilic CD-Man7, amphiphilic C3-CD-Man7 can self-assemble to form nanoparticles (CD-Man-NPs) in aqueous solution. Further, in vitro results confirmed that multivalent mannose ligands of either CD-Man7 or CD-Man-NPs stimulated RAW264.7 macrophages to differentiate into the M2 phenotype, which promoted fibroblast migration via a paracrine mechanism. In vivo results confirmed that both CD-Man7 and CD-Man-NPs reduced the inflammatory response in wound tissue and accelerated wound healing. The present study demonstrates multivalent effects of CD-Man7 and CD-Man-NPs on M2 macrophage polarization, indicating the therapeutic potential of these β-cyclodextrin glycoconjugates in the treatment of inflammatory diseases and wound healing.

Oncolytic adenoviruses (OAs) have shown great potential for cancer viral gene therapy in clinical studies. To date, clinical trials have shown that the curative efficacy of OAs is still limited by hepatic sequestration and preexisting neutralizing antibodies (nAbs), which decrease the accumulation of the OAs in tumors. Herein, with the biosilicification method, we encapsulated an OA encoding the anticancer gene Trail (OA-Trail) with silica, which significantly improved virus distribution and tumor inhibition. In vitro and in vivo results indicated that compared with the native OA, biosilicified OA-Trail (OA-Trail@SiO2) showed significantly reduced viral clearance in the liver and evaded nAb degradation, inducing an efficacious anticancer effect under the premise of biocompatibility. These achievements present an alternative strategy involving biosilicification for enhanced OA-based cancer gene therapy.