Zhang, J., Wan, S., Zhou, H., Du, J., Li, Y., Zhu, H., Weng, L., Ding, X., & Wang, L. (2024). Programmed Nanocloak of Commensal Bacteria-Derived Nanovesicles Amplify Strong Immunoreactivity against Tumor Growth and Metastatic Progression. ACS Nano, 18(13), 9613–9626. https://doi.org/10.1021/acsnano.3c13194
Abstract:
Recent discoveries in commensal microbiota demonstrate the great promise of intratumoral bacteria as attractive molecular targets of tumors in improving cancer treatment. However, direct leveraging of in vivo antibacterial strategies such as antibiotics to potentiate cancer therapy often leads to uncertain effectiveness, mainly due to poor selectivity and potential adverse effects. Here, building from the clinical discovery that patients with breast cancer featured rich commensal bacteria, we developed an activatable biointerface by encapsulating commensal bacteria-derived extracellular vesicles (BEV) with a responsive nanocloak to potentiate immunoreactivity against intratumoral bacteria and breast cancer. We show that the interfacially cloaked BEV (cBEV) not only overcame serious systemic side responses but also demonstrated heightened immunogenicity by intercellular responsive immunogenicity, facilitating dendritic cell maturation through activating the cGAS-STING pathway. As a preventive measure, vaccination with nanocloaked cBEVs achieved strong protection against bacterial infection, largely providing prophylactic efficiency against tumor challenges. When treated in conjunction with immune checkpoint inhibitor anti-PD-L1 antibodies, the combined approach elicited a potent tumor-specific immune response, synergistically inhibiting tumor progression and mitigating lung metastases.
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Funding Info:
This research / project is supported by the NA - Leading-edge Technology Programme of Jiangsu Natural Science Foundation
Grant Reference no. : BK20212012
This research / project is supported by the NA - Natural Science Foundation
Grant Reference no. : 22207056, 62288102
This research / project is supported by the NA - Natural Science Foundation of Jiangsu Province
Grant Reference no. : BK20210580, BK20220384