Oxygen‐Generated Hierarchical‐Structured AuNRs@MnO2@SiO2 Nanocarrier for Enhanced NIR‐ and H2O2‐Responsive Mild‐Hyperthermia Photodynamic/Photothermal Combined Tumor Therapy

Abstract

AbstractTumor hypoxia greatly restricts photodynamic therapy (PDT) efficiency. Photothermal therapy (PTT) implemented at high temperatures induces local skin burning and surrounding tissue damage. Herein, an near‐infrared (NIR)‐ and H2O2‐double responsive heat‐ and O2‐generating core–shell–shell AuNRs@MnO2@SiO2 nanocarrier with Au nanorods (AuNRs) as core and MnO2 as sandwiched nanolayer is developed to realize enhanced photodynamic/photothermal combined tumor therapy at mild‐hyperthermia temperatures. Coating poly‐l‐lysine on AuNRs is capable of preventing AuNRs from aggregation and facilitating the on‐site growth of MnO2. The mesoporous SiO2 nanoshell provides large loading sites for payload indocyanine green (ICG). The MnO2 nanolayer greatly enhances the singlet oxygen (1O2) generation efficiency of ICG both in testing tubes and in cancer cells. Consequently, the O2‐enhanced PDT endows the AuNRs@MnO2@SiO2‐ICG nanoparticles (NPs) dramatically stronger antitumor effect both in vitro and in vivo. Their tumor growth inhibition ratio (67.6%) is significantly higher than that of AuNRs@SiO2‐ICG (28.5%) after one dose intratumor injection and NIR irradiation. Together with their good biosafety, the AuNRs@MnO2@SiO2‐ICG is promisingly translational. The multifunctionality should provide the AuNRs@MnO2@SiO2 NPs a nanocarrier platform for various therapeutic agents to modulate the tumor microenvironment and enhance tumor therapy efficiency.