Engineered bacterial outer membrane vesicles encapsulating oncolytic adenoviruses enhance the efficacy of cancer virotherapy by augmenting tumor cell autophagy.

Autor: Ban W; Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, 110016, Liaoning, China., Sun M; School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, 110016, Liaoning, China., Huang H; Department of Surgical Oncology and General Surgery, The First Hospital of China Medical University, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, China Medical University, Ministry of Education, Shenyang, 110001, Liaoning, China., Huang W; Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, 110016, Liaoning, China., Pan S; Department of Surgical Oncology and General Surgery, The First Hospital of China Medical University, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, China Medical University, Ministry of Education, Shenyang, 110001, Liaoning, China., Liu P; Department of Surgical Oncology and General Surgery, The First Hospital of China Medical University, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, China Medical University, Ministry of Education, Shenyang, 110001, Liaoning, China., Li B; Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, 110016, Liaoning, China., Cheng Z; Sino-British Research Centre for Molecular Oncology, National Centre for International Research in Cell and Gene Therapy, School of Basic Medical Sciences, Academy of Medical Sciences, Zhengzhou University, Zhengzhou, 450052, China., He Z; Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, 110016, Liaoning, China., Liu F; Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, 110016, Liaoning, China. fnliu@cmu.edu.cn.; Department of Surgical Oncology and General Surgery, The First Hospital of China Medical University, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, China Medical University, Ministry of Education, Shenyang, 110001, Liaoning, China. fnliu@cmu.edu.cn., Sun J; Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, 110016, Liaoning, China. sunjin@syphu.edu.cn.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2023 May 22; Vol. 14 (1), pp. 2933. Date of Electronic Publication: 2023 May 22.
DOI: 10.1038/s41467-023-38679-z
Abstrakt: Oncolytic adenovirus (Ad) infection promotes intracellular autophagy in tumors. This could kill cancer cells and contribute to Ads-mediated anticancer immunity. However, the low intratumoral content of intravenously delivered Ads could be insufficient to efficiently activate tumor over-autophagy. Herein, we report bacterial outer membrane vesicles (OMVs)-encapsulating Ads as microbial nanocomposites that are engineered for autophagy-cascade-augmented immunotherapy. Biomineral shells cover the surface antigens of OMVs to slow their clearance during in vivo circulation, enhancing intratumoral accumulation. After entering tumor cells, there is excessive H 2 O 2 accumulation through the catalytic effect of overexpressed pyranose oxidase (P 2 O) from microbial nanocomposite. This increases oxidative stress levels and triggers tumor autophagy. The autophagy-induced autophagosomes further promote Ads replication in infected tumor cells, leading to Ads-overactivated autophagy. Moreover, OMVs are powerful immunostimulants for remolding the immunosuppressive tumor microenvironment, facilitating antitumor immune response in preclinical cancer models in female mice. Therefore, the present autophagy-cascade-boosted immunotherapeutic method can expand OVs-based immunotherapy.
(© 2023. The Author(s).)
Databáze: MEDLINE
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