Tumor microenvironment (TME) responsive chemodynamic therapy (CDT) showed an important application in inhibiting tumor growth by producing the highly toxic hydroxyl radical (·OH), but insufficient hydrogen peroxide (H2O2) and overexpressed glutathione (GSH) limited its application. Herein, by integrating photothermal therapy (PTT) and CDT, a new kind of mesoporous polydopamine (MPDA)-based cascade-reaction nanoplatform (MPDA@AuNPs-Cu) was designed for enhanced antitumor therapy, in which ultrasmall gold nanoparticles (AuNPs) with glucose oxidase (GOx)-like activity were deposited on MPDA for providing H2O2, and Cu2+ was chelated for GSH-responsive Fenton-like reaction. It was demonstrated that the MPDA@AuNPs-Cu nanoprobe showed high photothermal conversion efficiency and excellent biocompatibility. Moreover, the MPDA@AuNPs-Cu nanoprobe exhibited strong ·OH generation because of H2O2 self-generation and photothermal stimulation. Importantly, compared with MPDA-Cu, MPDA@AuNPs-Cu exhibited enhanced in vitro and in vivo CDT/PTT performance, by which the tumor growth was completely inhibited, achieving TME-responsive antitumor efficacy.
Keywords: H2O2 self-generation; enhanced chemodynamic therapy; photothermal stimulation; photothermal therapy; tumor microenvironment.