Facile Synthesis of a H2O2-Responsive Alternating Copolymer Bearing Thioether Side Groups for Drug Delivery and Controlled Release

Abstract

A novel amphiphilic alternating copolymer with thioether side groups (P(MSPA-a-EG)) was synthesized through an amine-epoxy click reaction of 3-(methylthio)propylamine (MSPA) and ethylene glycol diglycidyl ether. P(MSPA-a-EG) was characterized in detail by nuclear magnetic resonance (NMR), gel permeation chromatography, Fourier transformed infrared, differential scanning calorimeter, and thermogravimetric analysis to confirm the successful synthesis. Due to its amphiphilic structure, P(MSPA-a-EG) could self-assemble into spherical micelles with an average diameter of about 151 nm. As triggered by H2O2, theses micelles could disassemble because hydrophobic thioether groups are transformed to hydrophilic sulfoxide groups in MSPA units. The oxidant disassemble process of micelles was systemically studied by dynamic light scattering, transmission electron microscopy, and 1H NMR measurements. The MTT assay against NIH/3T3 cells indicated that P(MSPA-a-EG) micelles exhibited good biocompatibility. Furthermore, they could be used as smart drug carriers to encapsulate hydrophobic anticancer drug doxorubicin (DOX) with 4.90% drug loading content and 9.81% drug loading efficiency. In vitro evaluation results indicated that the loaded DOX could be released rapidly, triggered by H2O2. Therefore, such a novel alternating copolymer was expected to be promising candidates for controlled drug delivery and release.