Phthalocyanine aggregates as semiconductor-like photocatalysts for hypoxic-tumor photodynamic immunotherapy
Hao Liu, Ziqing Li, Xiaojun Zhang, Yihui Xu, Guoyan Tang, Zhaoxin Wang, Yuanyuan Zhao, Mei‐Rong Ke, Biyuan Zheng, Shuping Huang, Jian‐Dong Huang, Xingshu Li
Abstract
Photodynamic immunotherapy (PIT) has emerged as a promising approach for efficient eradication of primary tumors and inhibition of tumor metastasis. However, most of photosensitizers (PSs) for PIT exhibit notable oxygen dependence. Herein, a concept emphasizing on transition from molecular PSs into semiconductor-like photocatalysts is proposed, which converts the PSs from type II photoreaction to efficient type I photoreaction. Detailed mechanism studies reveal that the nanostructured phthalocyanine aggregate (NanoNMe) generates radical ion pairs through a photoinduced symmetry breaking charge separation process, achieving charge separation through a self-substrate approach and leading to exceptional photocatalytic charge transfer activity. Additionally, a reformed phthalocyanine aggregate (NanoNMO) is fabricated to improve the stability in physiological environments. NanoNMO showcases significant photocytotoxicities under both normoxic and hypoxic conditions and exhibits remarkable tumor targeting ability. Notably, the NanoNMO-based photodynamic therapy and PD-1 checkpoint inhibitor-based immunotherapy synergistically triggers the infiltration of cytotoxic T lymphocytes into the tumor sites of female mice, leading to the effective inhibition of breast tumor growth. The efficiency of photosensitizers-based photodynamic immunotherapy for cancer treatment is conventionally restricted by the hypoxic tumor microenvironment and oxygen dependence. Here, the authors address these issues by developing a design strategy of converting molecular photosensitizers to semiconductor-like photocatalysts.