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Surface-Engineered Extracellular Vesicles with CDH17 Nanobodies to Efficiently Deliver Imaging Probes and Chemo-Photothermal Drugs for Gastric Cancer Theragnostic |
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| Authors: | Peng Xia Haitao Yuan Ming Tian Tianyu Zhong Rui Hou Xiaolong Xu Jingbo Ma Huifang Wang Zhifen Li Defa Huang Chengming Qu Lingyun Dai Chengchao Xu Chuanbin Yang Haibo Jiang Yuanqiao He Felix Rückert Zhijie Li Yufeng Yuan Jigang Wang |
| Affiliation: | 1. Shenzhen Institute of Respiratory Disease, and Shenzhen Clinical Research Centre for Respirology, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, Guangdong, 518020 P. R. China
Department of Hepatobiliary & Pancreatic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, 430062 P. R. China;2. Shenzhen Institute of Respiratory Disease, and Shenzhen Clinical Research Centre for Respirology, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, Guangdong, 518020 P. R. China;3. Department of Hepatobiliary & Pancreatic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, 430062 P. R. China;4. Laboratory Medicine, Gannan Medical University, Ganzhou, Jiangxi, 341000 P. R. China;5. Harry Perkins Institute of Medical Research, QEII Medical Centre and Centre for Medical Research, The University of Western Australia, Nedlands, WA, 6009 Australia;6. School of Chemistry and Chemical Engineering, Shanxi Datong University, Xing Yun Street, Pingcheng District, Datong, Shanxi Province, 037009 P. R. China;7. Department of Chemistry, The University of Hong Kong, Pok Fu Lam, Hong Kong, 999077 P. R. China;8. School of Medicine, Nanchang University, Nanchang, Jiangxi, 330031 P. R. China;9. Department of Visceral Surgery, Diakonissen Hospital, 67346 Speyer, Germany |
| Abstract: | Extracellular vesicles (EVs) are widely used as natural nanoparticles to deliver various cargos for disease diagnosis and therapy. However, unmodified EVs cannot efficiently transport the cargos to desired sites due to non-specific uptake. Here, a delivery system is designed to display nanobodies against cadherin 17 (CDH17) on the surface of EVs isolated from HEK-293 cells and loaded with dye Indocyanine green (ICG) and/or anti-cancer drug dinitroazetidine derivative RRx-001, a blocker for CD47/ signal regulatory protein alpha (SIRPα) axis. CDH17 is a promising target for gastric cancer (GC) therapy. In this study, ICG loaded in the EVs engineered with CDH17 nanobodies can realize rapid tumor imaging in a CDH17-positive GC model and can produce significant anti-tumor photothermal therapeutic (PTT) effect after irradiation. Meanwhile, PTT effect can induce immunogenic cell death and macrophage polarization from M2 to M1 phenotype. The engineered EVs loaded with RRx-001 can significantly repress GC tumor growth. Finally, dual loading of ICG/RRx-001 in engineered EVs show maximal anti-tumor efficacy in both cancer cell and patient-derived GC models after only single injection. Collectively, CDH17 nanobody-functionalized EVs loaded with ICG and/or RRx-001 hold great promise to image and treat GC by combining fluorescent dye-induced PTT with chemotherapy. |
| Keywords: | chemotherapy extracellular vesicles nanobodies photothermal therapy targeted delivery |