Yuanyuan Zhao, Yihui Xu, Jiale Wen, Hyunsun Jeong, Heejeong Kim, Xingshu Li, Juyoung Yoon
The characteristics of tumor cells and their microenvironment, including high rates of recurrence and metastasis, insufficient oxygen (O 2 ) supply, and the immunosuppressive microenvironment, severely limit the effectiveness of conventional photodynamic therapy for hypoxic tumors. Herein, we report an O 2 -independent nano-photocatalyst (NanoPcCu), rationally designed to provide near-infrared light induced self-adaptive photodynamic processes, enhancing the generation of type I reactive oxygen species (OH· and O 2 •– ) and thermal effects to promote photoimmunotherapeutic antitumor responses. Simple copper (Cu)(II) and amino modifications on phthalocyanine (Pc) endowed (i) the self-assembled metal-Pc complex (NanoPcCu) with remarkable photothermal and photoacoustic effects and (ii) photoredox performance to catalytically convert H 2 O 2 to highly toxic ·OH upon photooxidation between Cu(II) and Cu(I) under normoxic and hypoxic conditions. These features allowed NanoPcCu to achieve a prominent phototherapeutic response under normoxic and hypoxic conditions. Notably, NanoPcCu-mediated phototherapy not only suppresses tumor growth completely in a preclinical model but also activates antitumor immune responses through the synergistic effects of photoredox activity and photothermal therapy. This study provides a reliable method to develop transition metal Pc complexes as efficient phototheranostic agents to overcome the hypoxic and immunosuppressive microenvironment of solid tumors.