NIR-responsive hollow germanium nanospheres mediate photothermal/photodynamic therapy and restrain immunosuppression to cooperatively eradicate primary and metastatic tumors

Photothermal and photodynamic therapies (PTT and PDT) generating regional hyperpyrexia or reactive oxygen species (ROS) not only kill tumors within irradiated site, but also potentially suppress metastatic tumors far away from irradiated site by activation of antitumor immunity through inducing immunogenic cell death (ICD) (termed as abscopal effect). However, mono-PTT or mono-PDT are generally insufficient to produce intensive and long-lasting abscopal effect. Moreover, abundant immune suppressors within tumor microenvironment can offset ICD-induced antitumor effects that further cripple phototherapeutic efficacy. Towards effective eradication of both primary and metastatic tumors, it is necessary to combine photothermal and photodynamic antitumor effects as well as reverse immunosuppressive tumor microenvironment. Here, we report a hollow germanium nanosphere (HGNs) with both favorable photothermal and photodynamic effects. HGNs under near-infrared (NIR) irradiation generated hyperpyrexia and intracellular ROS, promoting ICD of tumor cells. Notably, HGNs-mediated photothermal and photodynamic effects reduce the expression of immunosuppressive indoleamine-2,3-dioxygenase (IDO), stemness-and invasion/migration-related genes. In preclinical tumor models, HGNs drives antitumor immunity by promoting effector T-cell infiltration and reducing immunosup-pressive regulatory T cells (Tregs) under NIR, thus eradicating both primary and distant tumors along with extension of animal survival. Thus, with good biosafety, HGNs demonstrates a great clinically-translational potential.

Automated summary

Photothermal and photodynamic therapies (PTT and PDT) can activate antitumor immunity and suppress metastatic tumors by inducing immunogenic cell death (ICD). However, mono-PTT or mono-PDT are generally insufficient and tumor microenvironment can offset the antitumor effects. In this study, a hollow germanium nanosphere (HGNs) with favorable photothermal and photodynamic effects was developed, promoting ICD of tumor cells and reversing immunosuppressive tumor microenvironment. HGNs effectively eradicated both primary and distant tumors and improved animal survival, showing great potential for clinical translation.