Reduction stimuli-responsive unimolecular polymeric prodrug based on amphiphilic dextran-framework for antitumor drug delivery
We report a new reduction-responsive amphiphilic polymeric prodrug based on a linear dextran (DEX) backbone, which was conjugated with an hydrophobic camptothecin (CPT) prodrug block and an hydrophilic poly[poly(ethylene glycol) methyl ether methacrylate] (POEGMA) block [DEX-PCPT- b -POEGMA (DCO)] by atom transfer radical polymerization (ATRP). This amphiphilic prodrug has a unique molecular structure with prominent features, including strong practicability for methacrylate prodrug monomer, high drug loading rate (up to 23 wt%), adjustable proportion of hydrophobic and hydrophobic portions, superior stability in aqueous solution, and easy access to cells. Introduction of a disulfide bond linker between the drug and the carrier can realize the function of reduction-responsive controlled drug-release. The experimental study indicated that the prodrug exhibited notable antitumor activity against HeLa cells and MCF-7 cells in vitro. Compared to similar DCO prodrug based on double carbon bond, the disulfide bond-conjugated DCO prodrug induced higher level of tumor cell apoptosis. Considering the drug-loading efficiency, micellar stability, cost of preparation and controlled drug release, the presented prodrug is more advantageous than traditional unimolecular prodrug and represents a promising approach for design of stimuli-responsive polymeric prodrug for effective cancer therapeutics.
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