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

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.