Polymer–Temozolomide Conjugates as Therapeutics for Treating Glioblastoma

Abstract

A series of polymer-drug conjugates based on 2-methacryloyloxyethyl phosphorylcholine (MPC) was prepared with the glioblastoma drug temozolomide (TMZ) as pendent groups. Random and block copolymers were synthesized by reversible addition-fragmentation chain-transfer (RAFT) polymerization using a TMZ-containing methacrylate monomer. The solution properties of the polyMPC-TMZ copolymers were investigated by dynamic light scattering and transmission electron microscopy, revealing well-defined nanostructures from the block copolymers. Conjugation of TMZ to polyMPC enhanced drug stability, with decomposition half-life values ranging from 2- to 19-times longer than that of free TMZ. The cytotoxicity of polyMPC-TMZ was evaluated in both chemosensitive (U87MG) and chemoresistant (T98G) glioblastoma cell lines. Furthermore, the polyMPC-TMZ platform was expanded considerably by the preparation of redox-sensitive polyMPC-TMZ copolymers utilizing disulfides as the polymer-to-drug linker.