In Situ Photocatalyzed Oxygen Generation with Photosynthetic Bacteria to Enable Robust Immunogenic Photodynamic Therapy in Triple‐Negative Breast Cancer

• Published in: Advanced functional materials 2020-03, Vol.30 (10), p.n/a
• Main Authors: Liu, Lanlan, He, Huamei, Luo, Zhenyu, Zhou, Haimei, Liang, Ruijing, Pan, Hong, Ma, Yifan, Cai, Lintao
• Format: Article
• Language: English
• Subjects: Anticancer properties; Bacteria; Biomimetics; Breast cancer; Crosslinking; Hypoxia; immunogenic photodynamic therapy; Irradiation; Materials science; Metastasis; metastasis cancer; Nanoparticles; Oxygen; photocatalyzed oxygen; Photodynamic therapy; Photosynthesis; photosynthetic bacteria; tumor hypoxia; Tumors
• ISSN: 1616-301X; 1616-3028
• DOI: 10.1002/adfm.201910176

Hypoxia in the tumor microenvironment is a major hurdle dampening the antitumor effect of photodynamic therapy (PDT). Herein, active photosynthetic bacteria (Synechococcus 7942, Syne) are utilized for tumor‐targeted photosensitizer delivery and in situ photocatalyzed oxygen generation to achieve photosynthesis‐boosted PDT. Photosensitizer‐encapsulated nanoparticles (HSA/ICG) are assembled by intermolecular disulfide crosslinking and attached to the surface of Syne with amide bonds to form a biomimetic system (S/HSA/ICG). S/HSA/ICG combined the photosynthetic capability of Syne and the theranostic effect of HSA/ICG. Syne capable of photoautotrophy exhibit a moderate immune stimulation effect and a certain photodynamic role under 660 nm laser irradiation. Upon intravenous injection into tumor‐bearing mice, S/HSA/ICG can effectively accumulate in tumors and generate oxygen continuously under laser irradiation through photosynthesis, which remarkably relieve tumor hypoxia and enhance reactive oxygen species production, thereby completely eliminating primary tumors. This photosynthesis‐boosted PDT can also effectively reverse the tumor immunosuppressive microenvironment and robustly evoke systematic antitumor immune responses, which exhibit excellent effect on preventing tumor recurrence and metastasis inhibition in a metastatic triple‐negative breast cancer mouse model. Hence, this photosynthetic bacteria‐based photosynthesis‐boosted immunogenic PDT offers a promising approach to eliminate both local and metastatic tumors. The present study reports the use of active photosynthetic bacteria (Syne)‐delivered HSA/ICG NPs (S/HSA/ICG) for in situ photocatalyzed oxygen generation, which enable robust immunogenic PDT against tumor growth and metastasis. This photosynthesis‐boosted PDT can effectively improve the tumor immunosuppressive microenvironment and robustly evoke systematic antitumor immune responses, which exhibit excellent results for tumor recurrence and metastasis inhibition.