An effective, nontoxic,
tumor-specific
immunotherapy is the ultimate goal in the battle against
cancer, especially the metastatic disease. Checkpoint blockade-based
immunotherapies have been shown to be extraordinarily effective but benefit only the minority of patients whose
tumors have been pre-infiltrated by T cells. Here, we show that Zn-
pyrophosphate (
ZnP) nanoparticles loaded with the
photosensitizer pyrolipid (
ZnP@pyro) can kill
tumor cells upon irradiation with light directly by inducing apoptosis and/or
necrosis and indirectly by disrupting
tumor vasculature and increasing
tumor immunogenicity. Furthermore, immunogenic
ZnP@pyro
photodynamic therapy (
PDT) treatment sensitizes
tumors to checkpoint inhibition mediated by a PD-L1 antibody, not only eradicating the primary 4T1
breast tumor but also significantly preventing
metastasis to the lung. The abscopal effects on both 4T1 and TUBO bilateral syngeneic mouse models further demonstrate that
ZnP@pyro
PDT treatment combined with anti-PD-L1 results in the eradication of light-irradiated primary
tumors and the complete inhibition of untreated distant
tumors by generating a systemic
tumor-specific cytotoxic T cell response. These findings indicate that nanoparticle-mediated
PDT can potentiate the systemic efficacy of checkpoint blockade
immunotherapies by activating the innate and adaptive immune systems in tumor microenvironment.