Reduction-responsive disulfide linkage core-cross-linked polymeric micelles for site-specific drug delivery

Abstract

Biodegradable polymeric nanoparticles have attracted much attention in chemotherapy. However, premature drug release before reaching the target tissues and insufficient drug release within the target cells limit their further application. In this study, reduction-sensitive disulfide linkage core-cross-linked polymeric (mPEG_2k-b-PLL/LA) micelles were developed. Doxorubicin (DOX) as a model drug was encapsulated into the micelles. After core-cross-linking, the DOX-loaded polymeric micelles (CLM@DOX) can avoid premature drug release in the physiological environment and be triggered to dissociate in response to a high level of reductants of cancer cells. As expected, the reduction-sensitive CLM@DOX can rapidly release the drug intracellularly and lead to enhanced growth inhibition against glutathione-pretreated cancer cells. Notably, CLM@DOX exhibited the best in vivo antitumor capacity and reduced system toxicity compared with those of free DOX and uncross-linked UCLM@DOX groups, suggesting that this polymeric nanoparticle may have the potential to be applied as an effective site-specific drug delivery system for cancer treatment.