Qiu, X. et al., Biomacromolecules, 2022, 4519–4531,
https://pubs.acs.org/doi/10.1021/acs.biomac.2c00656
Chemodynamic therapy (CDT) reflects an innovative cancer treatment modality. To enhance its relatively low therapeutic efficiency, rational combination with extra therapeutic modes is highly appreciated. Here, core-coordinated amphiphilic, elliptic polymer nanoparticles (Cu/CBL–POEGEA NPs) are constructed via the self-assembly of a glutathione (GSH)-responsive polymer–drug conjugate. Side-chain acylthiourea (ATU) motifs are affixed, which behave as ligands capable of coordinating Cu(II). Benefitting from the GSH-induced reduction reaction, Cu(II) is converted into Cu(I) and subsequently react with endogenous H2O2 to create •OH, realizing GSH-depletion-promoted CDT. Additionally, the disulfide bond endows GSH-responsive CBL release and provokes further GSH decline, finally realizing combined CDT/CT toward enhancing antitumor outcomes, and in vitro as well as in vivo studies indeed reveal remarkable efficacy. Copyright © 2022, American Chemical Society.