Polymer–Temozolomide Conjugates as Therapeutics for Treating Glioblastoma

[Image: see text] 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.