Mesoporous polydopamine-based nanoplatform for enhanced tumor chemodynamic therapy through the reducibility weakening strategy.

Polydopamine (PDA)-based Fenton agents attract increasing attention in tumor photothermal-enhanced chemodynamic therapy (CDT) due to their good biocompatibility and excellent loading capacity. However, PDA tends to eliminate the Fenton reaction-generated hydroxyl radical (∙OH) by its strong reducibility, which is an intractable hinder to the efficacy of CDT that need to be solved. Herein, a kind of mesoporous PDA-gold-manganese dioxide (MPDA-Au-MnO, MPAM) nanoplatform was constructed for photothermal-enhanced CDT against tumor through the reducibility weakening strategy. The reducibility of original MPDA is effectively weakened by the oxidation role of HAuCl and KMnO during the preparation process, reducing the ∙OH scavenging ability of MPDA and benefiting the production of ∙OH. The MnO shell could react with GSH to release Mn, acting as the Fenton-like agent to generate ∙OH. The exposed Au NPs can further deplete GSH through the Au-S bond interaction. MPDA acts as the photothermal agent to generate hyperthermia under laser irradiation. MPAM shows excellent intracellular GSH scavenging ability and enhanced ∙OH production ability. After intravenous injection, MPAM can significantly suppress the growth of tumors under laser irradiation, meanwhile showing good biosafety. The developed MPDA-based nanoplatform can not only display good potential in further tumor treatments but also provide meaningful enlightenment for developing high-performance PDA or MPDA-based nanoplatforms in CDT-related applications.