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

Abstract Tumor 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 H 2 O 2 ‐double responsive heat‐ and O 2 ‐generating core–shell–shell AuNRs@MnO 2 @SiO 2 nanocarrier with Au nanorods (AuNRs) as core and MnO 2 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 MnO 2 . The mesoporous SiO 2 nanoshell provides large loading sites for payload indocyanine green (ICG). The MnO 2 nanolayer greatly enhances the singlet oxygen ( 1 O 2 ) generation efficiency of ICG both in testing tubes and in cancer cells. Consequently, the O 2 ‐enhanced PDT endows the AuNRs@MnO 2 @SiO 2 ‐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@SiO 2 ‐ICG (28.5%) after one dose intratumor injection and NIR irradiation. Together with their good biosafety, the AuNRs@MnO 2 @SiO 2 ‐ICG is promisingly translational. The multifunctionality should provide the AuNRs@MnO 2 @SiO 2 NPs a nanocarrier platform for various therapeutic agents to modulate the tumor microenvironment and enhance tumor therapy efficiency.