Synthesis and thermo-responsive self-assembly behavior of amphiphilic copolymer β-CD–(PCL–P(MEO2MA-co-PEGMA))21 for the controlled intracellular delivery of doxorubicin

Abstract

Well-defined amphiphilic β-cyclodextrin (β-CD) star-shaped copolymers with poly(ε-caprolactone)–poly(2-(2-methoxyethoxy)ethyl methacrylate)-co-poly(ethylene glycol)methacrylate) (β-CD–(PCL–P(MEO₂MA-co-PEGMA))₂₁ were synthesized via ring opening polymerization (ROP) and atom transfer radical polymerization (ATRP). These thermo-responsive copolymers exhibited a lower critical solution temperature (LCST) in water, which could be finely tuned by changing the feed ratio of PEGMA and MEO₂MA. The LCST of star-shaped β-CD–(PCL–P(MEO₂MA-co-PEGMA))₂₁ increased from 26 to 62 °C with the increasing PEGMA content, the copolymers were characterized using Fourier transform infrared spectroscopy (FTIR), proton nuclear magnetic resonance (¹H NMR) and gel permeation chromatography (GPC). The star-shaped copolymers could self-assemble into micelles in aqueous solution due to their amphiphilic properties resulting from the hydrophobic β-CD and PCL core and the hydrophilic P(MEO₂MA-co-PEGMA) segments, which was investigated by dynamic light scattering (DLS) and transmission electron microscopy (TEM). The in vitro DOX release studies showed that DOX released from drug-loaded micelles in a thermo-sensitive manner. CCK-8 assays demonstrated that these star-shaped copolymers could possess low cytotoxicity against HeLa cells, and the DOX-loaded micelles exhibited a higher inhibition of the proliferation of HeLa cells in comparison with free DOX. Moreover, the results from confocal laser scanning microscopy (CLSM) revealed that these polymeric micelles could efficiently deliver and release DOX into the nuclei of HeLa cells. This kind of biodegradable, biocompatible and stimuli-responsive copolymer could serve as a promising material for drug delivery.