Phthalocyanine aggregates as semiconductor-like photocatalysts for hypoxic-tumor photodynamic immunotherapy

Hao Liu, Ziqing Li, Xiaojun Zhang, Yihui Xu, Guoyan Tang, Zhaoxin Wang, Yuan-Yuan Zhao, Mei-Rong Ke, Bi-Yuan Zheng, Shuping Huang, Jian-Dong Huang () and Xingshu Li ()
Additional contact information
Hao Liu: Fuzhou University
Ziqing Li: Fuzhou University
Xiaojun Zhang: Fuzhou University
Yihui Xu: Fuzhou University
Guoyan Tang: Fuzhou University
Zhaoxin Wang: Fuzhou University
Yuan-Yuan Zhao: Fuzhou University
Mei-Rong Ke: Fuzhou University
Bi-Yuan Zheng: Fuzhou University
Shuping Huang: Fuzhou University
Jian-Dong Huang: Fuzhou University
Xingshu Li: Fuzhou University

Nature Communications, 2025, vol. 16, issue 1, 1-15

Abstract: 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.

Date: 2025
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DOI: 10.1038/s41467-024-55575-2

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