title: Enhancement of cellular uptake and antitumor efficiencies of micelles with phosphorylcholine.
abstract: Internalization of drug delivery micelles into cancer cells is a crucial step for antitumor therapeutics. Novel amphiphilic star-shaped copolymers with zwitterionic phosphorylcholine (PC) block, 6-arm star poly(ε-caprolactone)-b-poly(2-methacryloyloxyethyl phosphorylcholine) (6sPCL-b-PMPC), have been developed for encapsulation of poorly water-soluble drugs and enhancement of their cellular uptake. The star-shaped copolymers were synthesized by a combination of ring-opening polymerization (ROP) and atom transfer radical polymerization (ATRP). The copolymers self-assembled to form spherical micelles with low critical micelle concentration (CMC). The sizes of the micelles range from 80 to 170 nm and increase 30 ≈ 80% after paclitaxel (PTX) loading. Labeled with fluorescein isothiocyanate (FITC), the micelles were confirmed by fluorescence microscopy to have been internalized efficiently by tumor cells. Direct visualization of the micelles within tumor cells by transmission electron microscopy (TEM) confirmed that the 6sPCL-b-PMPC micelles were more efficiently uptaken by tumor cells compared to PCL-b-PEG micelles. When incorporated with PTX, the 6sPCL-b-PMPC micelles show much higher cytotoxicity against Hela cells than PCL-b-PEG micelles, in response to the higher efficiency of cellular uptake.
authors.affiliation: College of Polymer Science and Engineering, Sichuan University, Chengdu 610065, PR China.
authors.forename: Song
authors.initials: S
authors.lastname: Tu
authors.forename: Yuan-Wei
authors.initials: YW
authors.lastname: Chen
authors.forename: Yong-Bin
authors.initials: YB
authors.lastname: Qiu
authors.forename: Kun
authors.initials: K
authors.lastname: Zhu
authors.forename: Xiang-Lin
authors.initials: XL
authors.lastname: Luo
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D004705:Endocytosis / Q000187:drug effects*; D006367:HeLa Cells; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008689:Methacrylates / Q000138:chemical synthesis / Q000737:chemistry*; D008823:Micelles; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence; D017239:Paclitaxel / Q000494:pharmacology; D010767:Phosphorylcholine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D011091:Polyesters / Q000138:chemical synthesis / Q000737:chemistry; D011109:Polymethacrylic Acids
chemical_list: D000970:Antineoplastic Agents; D008689:Methacrylates; D008823:Micelles; D011091:Polyesters; D011109:Polymethacrylic Acids; C115766:poly(2-methacryloyloxyethyl-phosphorylcholine); D010767:Phosphorylcholine; C016240:polycaprolactone; D017239:Paclitaxel