Multi-responsive core-crosslinked poly (thiolether ester) micelles for smart drug delivery

Herein, a kind of multi-responsive core-crosslinked poly (thiolether ester) micelles was facilely prepared for reactive oxygen species (ROS), acid and reduction sensitive drug delivery. Firstly, a hydroxyl-rich poly (thiolether ester) (PTE) was synthesized by the thiol-ene/thiol-expoxy polymerization using ethanedithiol (EDT) and glycidylmethacrylate (GMA) as monomers . The resultant PTE was then coupled with carboxyl terminated poly (ethylene glycol) (PEG) and lipoic acid (LA) to give the graft copolymer PTE- g -PEG-LA. The obtained PTE- g -PEG-LA could self-assemble into micelles in the aqueous media and turn into core-crosslinked nanoparticles in the presence of dithiothreitol (DTT) at pH ∼8.3.The core-crosslinked PTE- g -PEG-LA micelles showed more compact structure and higher drug loading efficiency towards the model drug doxorubicin (DOX) as compared with non-crosslinked PTE- g -PEG micelles. In vitro drug release profiles demonstrated that the release of drug from DOX-loaded core-crosslinked PTE- g -PEG-LA micelles (CNP/DOX) could be accelerated in the ROS-abundant, acidic or reductive environment. The triggered release of loading drug from CNP/DOX in A549 and HeLa cells were also verified by laser scanning confocal microscopy , flow cytometry and cell proliferation inhibition assessments. These results indicate that the cross-linked PTE- g -PEG-LA micelles may provide huge potential for smart drug delivery in cancer therapy.