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: Song Tu, Yuan-Wei Chen, Yong-Bin Qiu, Kun Zhu, Xiang-Lin Luo
• Journal: Macromolecular bioscience (Macromol Biosci) Vol. 11 Issue 10 Pg. 1416-25 (Oct 10 2011) ISSN: 1616-5195 [Electronic] Germany
• PMID: 21793214 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Chemical References

• Antineoplastic Agents
• Methacrylates
• Micelles
• Polyesters
• Polymethacrylic Acids
• poly(2-methacryloyloxyethyl-phosphorylcholine)
• Phosphorylcholine
• polycaprolactone
• Paclitaxel

Topics

• Antineoplastic Agents (pharmacology)
• Cell Death (drug effects)
• Endocytosis (drug effects)
• HeLa Cells
• Humans
• Magnetic Resonance Spectroscopy
• Methacrylates (chemical synthesis, chemistry)
• Micelles
• Microscopy, Electron, Transmission
• Microscopy, Fluorescence
• Paclitaxel (pharmacology)
• Phosphorylcholine (analogs & derivatives, chemical synthesis, chemistry)
• Polyesters (chemical synthesis, chemistry)
• Polymethacrylic Acids