Tumor Microenvironment-Responsive MnO_<i>x</i>‑Mesoporous Carbon Nanoparticles for EnhancedChemodynamic Synergistic Antitumor Therapy

Developing nanomedicines with simultaneous diagnosis and treatment functions is a promising therapeutic strategy for cancer therapy. Herein, multifunctional manganese oxide-mesoporous carbon nanoparticles (MnO<i>_x</i>-MCN NPs) were designed for magnetic resonance imaging (MRI)-guided chemotherapy, photothermal therapy (PTT), and chemodynamic therapy (CDT). The excellent photothermal conversion efficiency (44.2%) and outstanding fenton-like catalytic activity endowed MnO<i>_x</i>-MCN NPs with a PTT/CDT synergistic therapy. Furthermore, with their unique mesoporous structure, MnO<i>_x</i>-MCN NPs can also act as a drug delivery carrier for encapsulating chemotherapy agent doxorubicin (DOX). The mild acid tumor microenvironment (TME) and near-infrared (NIR) heat induced the release of DOX. In addition, the NIR laser enhanced the CDT efficiency of MnO<i>_x</i>-MCN NPs, thus generating a synergistic chemotherapy/PTT/CDT effect. Extracellular experiments demonstrated that the heat generated by laser irradiation of MnO<i>_x</i>-MCN NPs could encourage the generation of ^•OH. More importantly, MnO<i>_x</i>-MCN NPs displayed a superior synergistic anticancer efficiency both in vitro and in vivo. Such elaborately synthesized nanomaterial provides a paradigm for the design of other multifunction nanoagents.