Phosphorylcholine zwitterionic shell-detachable mixed micelles for enhanced cancerous cellular uptakes and increased DOX release

To further enhance the cancerous cellular uptakes and increase the drug release of the drug loaded micelles, herein, we fabricated a series of mixed micelles with different mass ratios using two amphiphilic copolymers P(DMAEMA-co-MaPCL) and PCL-SS-PMPC. The mixed micelles showed a prolonged circulation time due to the zwitterionic shells in a physiological environment (pH 7.4). In addition, because of the protonation of tertiary amine groups in PDMAEMA and the breakage of the disulfide bond in PMPC-SS-PCL in a tumor microenvironment, the mixed micelles aggregated, which led to enhanced cancerous cellular penetration and increased DOX release. Moreover, cytotoxicity assay showed that the mixed micelles had good biocompatibility to L929, HeLa and MCF-7 cells, even at a concentration of up to 1 mg mL^-1. Furthermore, enhanced antitumour activity and cellular uptake of HeLa and MCF-7 cells were detected after loading with DOX, which was determined by confocal laser scanning microscopy (CLSM) and flow cytometry (FC), especially for the DOX@MIX 3 micelles (20% mass ratio of the P(DMAEMA-co-MaPCL)). Therefore, the mixed strategy provides a simple and efficient ways to promote anticancer drug delivery.