pH- and Reduction-Responsive Polymeric Lipid Vesicles for Enhanced Tumor Cellular Internalization and Triggered Drug Release

Enhanced tumor cellular internalization and triggered drug release are two main concerns in the development of nanoparticles for antitumor drug delivery. In this article, a new kind of smart pH- and reduction-dual-responsive drug- loaded PEG coated polymeric lipid vesicle (PPLV) that can achieve both enhanced tumor cellular internalization and triggered drug release has been designed and prepared. The PPLVs were formed from amphiphilic dextran derivatives. The antitumor drug, doxorubicin (DOX), was loaded in the cores of the PPLVs. The newly developed PPLVs had a nanosized structure (similar to 40 nm) with PEG coating, so they were neutral and had high colloidal stability in the blood circulation. The in vitro physicochemical characterizations showed that the PPLVs lose their PEG coating and expose the positive surface charge under acidic environments. The in vitro cellular uptake study indicated that the acidic-treated PPLVs can efficiently enter tumor cells. It has been demonstrated by in vitro DOX release profiles that the PPLVs can achieve a triggered drug release in response to the reduction environment. The MTT assay demonstrated that DOX-loaded PPLVs treated with pH 5.0 solution had higher antitumor activity than DOX-loaded PPLVs treated with pH 7.4 solution. These results suggested that the PPLVs were promising nanoparticles for smart antitumor drug delivery applications.