State Key Laboratory of Digital Medical Engineering, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering, Southeast University, 2 Southeast University Road, Nanjing, 211189, P. R. China.
Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, P. R. China.
Nat Commun. 2024 Jun 17;15(1):5147. doi: 10.1038/s41467-024-49156-6.
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.
由于细菌具有内在的肿瘤趋向性，细菌介导的癌症治疗策略引起了越来越多的关注。然而，基于细菌的药物面临着几个挑战，包括细菌的体积大和细胞外基质的密集，限制了它们在肿瘤内的输送效率。在这项研究中，我们发现高压氧（HBO），一种非侵入性的治疗方法，可以有效地耗尽密集的细胞外基质，从而增强肿瘤内细菌的积累。受此发现的启发，我们用 cypate 分子修饰大肠杆菌 Nissle 1917（EcN），得到 EcN-cypate 用于光热治疗，随后可以诱导免疫原性细胞死亡（ICD）。重要的是，HBO 治疗显著增加了 EcN-cypate 在肿瘤内的积累，并促进了免疫细胞在肿瘤内的浸润，通过光热治疗和 ICD 诱导的免疫治疗实现了理想的肿瘤清除。我们的工作提供了一种简便、非侵入性的策略来提高天然/工程细菌的肿瘤内输送效率，并可能促进细菌介导的协同癌症治疗的临床转化。
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