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 H2O2-double responsive heat- and O-2-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 (O-1(2)) generation efficiency of ICG both in testing tubes and in cancer cells. Consequently, the O-2-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.

Automated summary

In this study, a nanocarrier was developed to enhance photodynamic and photothermal combined tumor therapy. The nanocarrier has double responsive characteristics, generating heat and O-2 at mild-hyperthermia temperatures. It demonstrated strong anti-tumor effects in testing and showed good biosafety. The multifunctional nanocarrier provides a platform for various therapeutic agents to modulate the tumor microenvironment and enhance tumor therapy efficiency.