Cellular uptake of pH/reduction responsive phosphorylcholine micellesElectronic supplementary information (ESI) available. See DOI: 10.1039/c7nj02484c

Phosphorylcholine micelles based on pH/reduction responsive copolymers, poly( -caprolactone)-ss- b -poly(( N , N -diethylaminoethyl methacrylate)- r -poly(2-methacryloyloxyethyl phosphorylcholine)) (PCL-ss-PDEAPMPC) were developed for the intracellular delivery of doxorubicin. The micelles were spherical (less than 90 nm in diameter) and demonstrated pH/reduction sensitivity. The DOX loaded micelles presented the fastest drug release under simultaneously acidic and reductive conditions. Although PCL 20 -ss-PDEA 5 PMPC 10 had lower pH sensitivity than PCL 20 -ss-PDEA 15 PMPC 10 , the DOX loaded micelles of the former released the drug faster than the latter at pH 5.0 and in the presence of a reductant. The cytotoxicities of the blank micelles and the drug-loaded micelles were investigated using the human cervical cancer cell line (HeLa). The IC 50 (half maximal inhibitory concentration) of PCL 20 -ss-PDEA 5 PMPC 10 micelles was the lowest among PCL-ss-PDEAPMPC micelles. The results of CLSM and flow cytometry showed that the micelles effectively delivered the drug cargo into cancer cells. The cellular uptake pathways of PCL-ss-PDEAPMPC micelles were mainly clathrin-mediated endocytosis, and accompanied by a certain degree of giant pinocytosis. We study the relationship between the PDEA content and internalization/intracellular drug release of pH responsive phosphorylcholine micelles as drug carriers.