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pH/redox dual-sensitive platinum (IV)-based micelles with greatly enhanced antitumor effect for combination
1Engineering Research Center for Biomedical Materials, School of Life Science, Anhui Key Laboratory of Modern Biomanufacturing, Anhui University, 111 Jiu long Road, Hefei, Anhui Province 230601, PR China.
Abstract:
To achieve precise control of nano-carrier structure and drug release behavior, we designed a pH/redox dual-responsive polymeric prodrug by condensation polymerization using octahedrally coordinated cisplatin (Pt IV) and ortho ester monomer. The prodrug was then self-assembled with doxorubicin (DOX) in aqueous solution to give a synergetic drug delivery system. The polymer backbone can completely degrade and release cisplatin (Pt II) and DOX under the acidic and reductive environment of tumor cells, owing to the breakage of ortho ester bonds and the reduction of Pt (IV). The size and micromorphology of micelles were observed by dynamic light scattering (DLS) and transmission electron microscopy (TEM). In vitro study of drug release, cellular uptake and cytotoxicity revealed that the micelles could be triggered intracellularly to release two drugs. In vivo drug distribution and antitumor activity also provide the evidence for the excellent antitumor effect of micelles.
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