Cellular uptake of pH/reduction responsive phosphorylcholine micelles. (18th September 2017)

• Record Type: Journal Article
• Authors: Cai, Yuanyuan; Li, Shuai; Cai, Mengtan; Chen, Yuanwei; Luo, Xianglin
• Is Part Of: New journal of chemistry. Volume 41:Number 20(2017)
• Page Start: 11828
• Page End: 11838
• Publication Date: 2017-09-18
• Subjects: Chemistry -- Periodicals; Chimie -- Périodiques; 540
• DOI: 10.1039/c7nj02484c
• Languages: English
• ISSNs: 1144-0546

Abstract

Abstract : We study the relationship between the PDEA content and internalization/intracellular drug release of pH responsive phosphorylcholine micelles as drug carriers. Abstract : Phosphorylcholine micelles based on pH/reduction responsive copolymers, poly(ε-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 PCL20 -ss-PDEA5 PMPC10 had lower pH sensitivity than PCL20 -ss-PDEA15 PMPC10, 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 IC50 (half maximal inhibitory concentration) of PCL20 -ss-PDEA5 PMPC10 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.