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World J Gastrointest Oncol. Jun 15, 2026; 18(6): 117697
Published online Jun 15, 2026. doi: 10.4251/wjgo.v18.i6.117697
Published online Jun 15, 2026. doi: 10.4251/wjgo.v18.i6.117697
Low-pH preconditioned macrophage-derived extracellular vesicles enable targeted and enhanced paclitaxel therapy in gastric cancer
Jing-Hui Wang, Ming-Li Hu, Min Shi, Jia-Li Ma, Yu-Gang Wang, Department of Gastroenterology, Tong Ren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200336, China
Jing Yang, Department of Pathology, Tong Ren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200336, China
Yu-Gang Wang, Key Laboratory for Translational Research and Innovative Therapeutics of Gastrointestinal Oncology, Tong Ren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200336, China
Co-first authors: Jing-Hui Wang and Ming-Li Hu.
Co-corresponding authors: Jing Yang and Yu-Gang Wang.
Author contributions: Wang JH and Hu ML contributed equally to this work as co-first authors; Wang JH and Hu ML were responsible for the study conception and design, performed the majority of experiments, analyzed the data, and drafted the initial manuscript; Shi M and Ma JL participated in experimental execution, data collection, and data organization; Yang J and Wang YG provided overall experimental guidance and research resources, supervised the project, critically revised and proofread the manuscript, and contributed equally as co-corresponding authors; and all authors reviewed and approved the final manuscript.
Supported by Natural Science Foundation of the Science and Technology Commission of Shanghai Municipality, No. 23ZR1458300 (to Wang YG); Key Discipline Project of Shanghai Municipal Health System, No. 2024ZDXK0004 (to Shi M); Special Project for Clinical Research in Health Industry of Shanghai Municipal Health Commission, No. 20254Y0097 (to Wang JH); Youth Project Fund of Changning District Health Commission, No. 2024QN02 (to Wang JH); and Research Fund of Key Laboratory for Translational Research and Innovative Therapeutics of Gastrointestinal Oncology, No. ZDSYS-2023-04 (to Wang JH).
Institutional animal care and use committee statement: This study was performed in strict accordance with the Regulations for the Care and Use of Laboratory Animals and the Guidelines for Ethical Review of Animal Experiments (China, GB/T 35892-2018). All procedures involving animals were reviewed and approved by Ethics Committee of Shanghai Tong Ren Hospital (approval number: A2023-004-01).
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Data sharing statement: Dataset available from the corresponding author at wyg0061@shtrhospital.com.
Corresponding author: Yu-Gang Wang, MD, Professor, Department of Gastroenterology, Tong Ren Hospital, Shanghai Jiao Tong University School of Medicine, No. 1111 Xianxia Road, Changning District, Shanghai 200336, China. wyg0061@shtrhospital.com
Received: December 24, 2025
Revised: January 21, 2026
Accepted: February 25, 2026
Published online: June 15, 2026
Processing time: 175 Days and 18.2 Hours
Revised: January 21, 2026
Accepted: February 25, 2026
Published online: June 15, 2026
Processing time: 175 Days and 18.2 Hours
Core Tip
Core Tip: In this study, we report a microenvironment-inspired strategy to customize macrophage-derived extracellular vesicles (EVs) through low-pH preconditioning, mimicking the acidic characteristics of the tumor microenvironment. This approach markedly enhances EVs' tumor targeting and endows them with a distinct miRNA cargo associated with reported anti-tumor functions. When used as nanocarriers for paclitaxel (PTX), the resulting biomimetic system (PTX@LP-EV) achieves superior anti-tumor efficacy in gastric cancer models. Mechanistically, EV-borne miRNAs induced by tumor microenvironmental stimulation may cooperatively suppress pro-tumorigenic genes, which is consistent with the observed enhanced therapeutic effects.