Construction of Folate-Conjugated and pH-Responsive Cell Membrane Mimetic Mixed Micelles for Desirable DOX Release and Enhanced Tumor-Cellular Target

Smart multifunctional polymeric micelles are in urgent demand for future cancer diagnosis and therapy. In this paper, doxorubicin (DOX)-loaded folic acid (FA)-targeting and pH-responsive cell membrane mimetic mixed micelles of P(DMAEMA-co-MaPCL) (PCD) and FA-P(MPC-co-MaPCL) (PMCF) (mass ratio 5/5) were prepared by a dialysis method. The micelle size, morphology, X-ray powder diffraction (XRD), pH responsiveness, in vitro DOX release, cytotoxicity, and cellular uptake were studied in detail. The results indicated that DOX could be efficiently loaded into mixed micelles (PDMCF micelles), and the DOX-loaded mixed micelles (DOX@PDMCF micelles) exhibited a size of 150 nm and pH-responsive DOX release in an extended period. Furthermore, the DOX@PDMCF micelles could efficiently suppress the proliferation of tumor cells, HeLa and MCF-7 cells. Our data suggest that the DOX@PDMCF micelles have the potential to be applied in tumor therapy, especially for treating various folate receptor overexpressed tumors.