Redox-responsive properties of core-cross-linked micelles of poly(ethylene oxide)-b-poly(furfuryl methacrylate) for anticancer drug delivery application

The design and fabrication of smart delivery systems that can efficiently deliver a payload to a targeted site in a controlled manner are immensely desirable in chemotherapy. We report the redox-responsive drug delivery property of core-cross-linked (CCL) micelles of poly(ethylene oxide)(5k)-b-poly(furfuryl methacrylate)(2k) (PEO5k-b-PFMA(2k)). The PEO5k-b-PFMA(2k) was prepared by using single electron transfer-living radical polymerization of furfuryl methacrylate (FMA) with a PEO-Br macro-initiator. Doxorubicin (DOX) was loaded into hydrophobic PFMA cores of the polymeric micelles, which were subsequently cross-linked with a diselenide-containing crosslinker, bis(maleimidoethyl) 3,3'-diselanediyldipropionoate via Diels-Alder reaction. Under physiological conditions, CCL micelles displayed increased structural stability, whereas the micelles showed a redox-responsive behavior when treated with 100 mM hydrogen peroxide (H2O2) and 10 mM glutathione (GSH). The CCL micelles were de-cross-linked due to the breaking of diselenide bonds present in the core-cross-linkages. DOX-loaded CCL micelles were stable at pH 7.4, while a higher DOX release was achieved at acidic pH 5.0 owing to the protonation of DOX. The DOX release was significantly enhanced in presence of 10 mM GSH or 100 mM H2O2 at pH 5.0 (which is a similar environment in tumor cells). The non-CCL and CCL micelles were found non-toxic to HFF-1 normal cells. However, DOX encapsulated CCL micelles showed remarkable cytotoxicity in HeLa cells. The confocal images showed that the DOX-loaded CCL micelles can quickly be internalized and efficiently deliver DOX into the HeLa cells.

Automated summary

This study reports on a redox-responsive core-cross-linked micelle that can efficiently deliver drugs. The micelle is structurally stable under physiological conditions but can release drugs under acidic and redox environments. The micelle shows no cytotoxicity towards normal cells but exhibits significant cytotoxicity towards cancer cells.