Hyperbaric oxygen enhances tumor penetration and accumulation of engineered bacteria for synergistic photothermal immunotherapy

Ke-Fei Xu, Shun-Yu Wu, Zihao Wang, Yuxin Guo, Ya-Xuan Zhu, Chengcheng Li, Bai-Hui Shan, Xinping Zhang, Xiaoyang Liu and Fu-Gen Wu ()
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Ke-Fei Xu: Southeast University
Shun-Yu Wu: Southeast University
Zihao Wang: Southeast University
Yuxin Guo: Southeast University
Ya-Xuan Zhu: Tongji University School of Medicine
Chengcheng Li: Nanjing Forestry University
Bai-Hui Shan: Southeast University
Xinping Zhang: Southeast University
Xiaoyang Liu: Southeast University
Fu-Gen Wu: Southeast University

Nature Communications, 2024, vol. 15, issue 1, 1-21

Abstract: Abstract Bacteria-mediated cancer therapeutic strategies have attracted increasing interest due to their intrinsic tumor tropism. However, bacteria-based drugs face several challenges including the large size of bacteria and dense extracellular matrix, limiting their intratumoral delivery efficiency. In this study, we find that hyperbaric oxygen (HBO), a noninvasive therapeutic method, can effectively deplete the dense extracellular matrix and thus enhance the bacterial accumulation within tumors. Inspired by this finding, we modify Escherichia coli Nissle 1917 (EcN) with cypate molecules to yield EcN-cypate for photothermal therapy, which can subsequently induce immunogenic cell death (ICD). Importantly, HBO treatment significantly increases the intratumoral accumulation of EcN-cypate and facilitates the intratumoral infiltration of immune cells to realize desirable tumor eradication through photothermal therapy and ICD-induced immunotherapy. Our work provides a facile and noninvasive strategy to enhance the intratumoral delivery efficiency of natural/engineered bacteria, and may promote the clinical translation of bacteria-mediated synergistic cancer therapy.

Date: 2024
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DOI: 10.1038/s41467-024-49156-6

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