Comparison of Biomimetic Block Copolymer Micelles as Drug Carriers for Cancer Therapy

Zwitterionic poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) is a promising alternative for poly(ethylene glycol) (PEG) as micelle shell-forming block. Three different PMPC-based polymeric micelles were designed and compared with PEGylated micelles. Cholesterol-conjugated and disulfide-modified poly(D, L-lactide)-SS-poly(2-methacryloyloxyethyl phosphorylcholine) (CPLA-SS-PMPC) micelles, cholesterol-conjugated CPLA-PMPC micelles without disulfides, and PLA-PMPC micelles without cholesterol-conjugation were compared to PLA-PEG micelles. These PMPC-based micelles showed better hydrophilicity and less protein adsorption. In cellular uptake evaluation, PMPC-based micelles exhibited much better cellular uptake than that of the PLA-PEG, which might reflect strong interaction between the biomimetic PMPC surface and the cellular membrane. In addition, although there was no statistical difference in cellular internalization behavior among these three PMPC-based micelles, the anticancer activity of paclitaxel (PTX)-loaded CPLA-SS-PMPC micelles was significantly higher than those of the other two kinds of micelles. This superiority was attributed to the rapid release of the anticancer drug under the redox environment inside cancer cells.