21:T4ac,A novel pH and reduction dual-responsive nanogel with improved cellular internalization was prepared through atom transfer radical polymerization and subsequent quaternization reaction. Doxorubicin (DOX), a model anticancer drug, was loaded into the nanogel via dispersion. The DOX-loaded nanogel presented a stable core-cross-linked structure under physiological conditions, but quickly released its payload in an acidic (pH 6.8) and reductive (10.0 mM glutathione) environment. Confocal fluorescence microscopy and fluorescence flow cytometry revealed that the DOX-loaded nanogel could deliver DOX into the cytoplasm and nucleus of cells, more efficiently than that of free DOX. The improved cellular internalization was more significant under acidic and reductive conditions, which was analogous to the pH and reductive conditions in endosomes and cytoplasm. In vitro cytotoxicity studies demonstrated that the pH and reduction responsive DOX-loaded nanogel could inhibit cellular proliferation more efficiently than free DOX. This dual-bioresponsive nanogel with quaternary ammonium salt group has appeared to be highly promising in the further development of intracellular drug transporters.22:T410,Rheumatoid arthritis (RA) is a chronic autoimmune disorder implicated in multiple joint affection and even disability. The activated macrophages perform a predominant role in onset and persistence of RA. Scavenger receptor (SR), one of several receptors overexpressed on the activated macrophages, is a specific biomarker for targeted therapy of numerous chronic inflammation diseases like RA. In this work, dextran sulfate-graft-methotrexate conjugate (DS-g-MTX) is synthesized and characterized, which exhibits excellent targetability to SR on the activated RAW 264.7 cells. Additionally, the enhanced accumulation and potent inflammatory inhibition are observed in the affected joint after intravenous injection of DS-g-MTX, compared to the treatment with dextran-graft-methotrexate (Dex-g-MTX), as is confirmed by the detection of histopathology and pro-inflammatory cytokines. Our work highlights DS-g-MTX as a potential therapeutic option for RA aiming the SR-expressed activated macrophages.

	Year	Citations

References