Synthesis, self-assembly and drug release behaviors of a bottlebrush polymer-HCPT prodrug for tumor chemotherapy

A bottlebrush polymer-cytotoxin prodrug, where a potent anticancer drug 10-hydroxycamptothecin (HCPT) and water-soluble methoxypolyethylene glycols (mPEG) were attached into the polyester backbone, was synthesized via thiol-ene reaction. The synthesized bottlebrush polymer-HCPT conjugate with drug loading content as high as ca. 20.4 wt% was characterized by NMR, IR, UV and fluorescence techniques. The prepared bottlebrush polymer-HCPT prodrug could self-assemble into nanosized micelles (ca. 153 nm), which were uniform and stable in aqueous solution. Moreover, when exposed to esterase, the formed prodrug micelles as stimuli-responsive nanomaterials could release HCPT. In the cellar uptake and cytotoxicity experiments, the formed prodrug micelles exhibited effective internalization into tumor cells and excellent anticancer efficacies.