4.8 Article

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

Journal

ADVANCED FUNCTIONAL MATERIALS
Volume 30, Issue 10, Pages -

Publisher

WILEY-V C H VERLAG GMBH
DOI: 10.1002/adfm.201910176

Keywords

immunogenic photodynamic therapy; metastasis cancer; photocatalyzed oxygen; photosynthetic bacteria; tumor hypoxia

Funding

  1. National Natural Science Foundation of China [81801838, 31571013, 81701816, 81601552]
  2. Guangdong Natural Science Foundation of Research Team [2016A030312006]
  3. K.C. Wong Education Foundation [GJTD-2018-14]
  4. Natural Science Foundation of Guangdong Province [2018A030313013]
  5. Shenzhen Science and Technology Program [JCYJ20180302145912832, JCYJ20170818162259843, JCYJ20170818163739458]

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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.

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