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Recent research has focused on cell membrane-coated nanoparticles for targeted drug delivery, leveraging their ability to evade the immune system while selectively targeting tumor cells. In this study, we developed a biomimetic hybrid nanoplatform based on cell membranes to combine molecular chemotherapy and improve the effectiveness of immunochemotherapy in treating ESCC. The nanoplatform is coated with a membrane fusion of activated neutrophils and ESCC cells and loaded with paclitaxel (PTX) and small interfering RNA targeting EFNA1 (siEFNA1), a molecule linked to ESCC metastasis. By exploiting the homologous targeting properties of ESCC cell membranes and the tumor-homing ability of neutrophil membranes, the platform effectively targets ESCC tissues and delivers siEFNA1 and PTX. This allows for a synergistic treatment approach, combining EFNA1 gene silencing with PTX-induced cytotoxicity to target ESCC more effectively. Crucially, the nanoplatform reprograms tumor-associated macrophages from the pro-tumor M2 phenotype to the anti-tumor M1 phenotype while boosting T cell-mediated cytotoxicity and remodeling the immunosuppressive tumor microenvironment. Overall, this strategy presents a promising approach for the targeted treatment of ESCC.<\/jats:p>","DOI":"10.1021\/acsami.6c14588","type":"journal-article","created":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T11:02:11Z","timestamp":1791630131000},"page":"55910-55929","source":"Crossref","is-referenced-by-count":0,"title":["Bioengineered Hybrid Nanovesicles Modulate the Immune Microenvironment with Targeted Drug Delivery for Esophageal Squamous Cell Carcinoma Therapy"],"prefix":"10.1021","volume":"18","author":[{"given":"Fei","family":"Xie","sequence":"first","affiliation":[{"name":"The Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University, Northern Jiangsu Institute of Clinical Medicine, Nanjing Medical University , , , ,","place":["Huai'an, Jiangsu, China, 223300"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lulu","family":"Feng","sequence":"additional","affiliation":[{"name":"The Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University, Northern Jiangsu Institute of Clinical Medicine, Nanjing Medical University , , , ,","place":["Huai'an, Jiangsu, China, 223300"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuting","family":"Wang","sequence":"additional","affiliation":[{"name":"The Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University, Northern Jiangsu Institute of Clinical Medicine, Nanjing Medical University , , , ,","place":["Huai'an, Jiangsu, China, 223300"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaofan","family":"Huang","sequence":"additional","affiliation":[{"name":"The Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University, Northern Jiangsu Institute of Clinical Medicine, Nanjing Medical University , , , ,","place":["Huai'an, Jiangsu, China, 223300"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenlong","family":"Wang","sequence":"additional","affiliation":[{"name":"The Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University, Northern Jiangsu Institute of Clinical Medicine, Nanjing Medical University , , , ,","place":["Huai'an, Jiangsu, China, 223300"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6233-3287","authenticated-orcid":true,"given":"Chao","family":"Luo","sequence":"additional","affiliation":[{"name":"The Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University, Northern Jiangsu Institute of Clinical Medicine, Nanjing Medical University , , , ,","place":["Huai'an, Jiangsu, China, 223300"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Zhang","sequence":"additional","affiliation":[{"name":"The Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University, Northern Jiangsu Institute of Clinical Medicine, Nanjing Medical University , , , ,","place":["Huai'an, Jiangsu, China, 223300"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Congyong","family":"Sun","sequence":"additional","affiliation":[{"name":"The Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University, Northern Jiangsu Institute of Clinical Medicine, Nanjing Medical University , , , ,","place":["Huai'an, Jiangsu, China, 223300"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5116-9186","authenticated-orcid":true,"given":"Qilong","family":"Wang","sequence":"additional","affiliation":[{"name":"The Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University, Northern Jiangsu Institute of Clinical Medicine, Nanjing Medical University , , , ,","place":["Huai'an, Jiangsu, China, 223300"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,10,10]]},"reference":[{"issue":"3","key":"2026102609074830500_cit1","doi-asserted-by":"publisher","first-page":"229","DOI":"10.3322\/caac.21834","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J. 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