pH-Sensitive Dextran-Based Micelles from Copper-Free Click Reaction for Antitumor Drug Delivery

There remains a need to develop new strategies to fabricate dextran-based biocompatible drug delivery systems for safe and effective chemotherapy. Herein, a copper-free azide-propiolate ester click reaction was introduced for dextran modification to fabricate a pH-sensitive dextran-based drug delivery system. A pH-sensitive dextran-based micelle system, self-assembled from amphiphilic dextran-graft-poly­(2-(diisopropylamino)­ethyl methacrylate-co-2-(2′,3′,5′-triiodobenzoyl)­ethyl methacrylate) or dextran-g-P­(DPA-co-TIBMA), is reported for effective chemotherapy. The amphiphilic dextran-g-P­(DPA-co-TIBMA) was prepared via reversible addition–fragmentation chain-transfer (RAFT) polymerization and copper-free azide-propiolate ester click reaction. Doxorubicin (DOX)-loaded dextran-g-P­(DPA-co-TIBMA) micelles were prepared through self-assembly of DOX and dextran-g-P­(DPA-co-TIBMA) in aqueous solution, and had a mean diameter of 154 nm and a drug loading content of 9.7 wt %. The release of DOX from DOX-loaded dextran-g-P­(PDPA-co-TIBMA) micelles was slow at pH 7.4, but was greatly accelerated under acidic conditions (pH 6 and 5). Confocal laser scanning microscopy and flow cytometry experiments showed that the dextran-g-P­(DPA-co-TIBMA) micelles could effectively deliver and release DOX in human breast cancer cell line (MCF-7 cells). MTT assay showed that dextran-g-P­(DPA-co-TIBMA) exhibited excellent biocompatibility while DOX-loaded dextran-g-P­(DPA-co-TIBMA) micelles have good antitumor efficacy in vitro. The in vivo therapeutic studies indicated that the DOX-loaded dextran-g-P­(PDPA-co-TIBMA) micelles could effectively reduce the growth of tumor with little body weight reduction.