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Cell membrane\u2010coated nanoparticles (CMNPs) obtain extra targeting, recognition, and signaling transduction functions. However, a single kind of CMNPs is limited when facing complicated tumor immunogene therapy. Here reported the collaboration of two types of CMNPs using a double\u2010layered spherical scaffold. This scaffold was prepared by stacking photosensitive hydrogels with two concentrations. After implantation, the two layers degraded successively within 5\u20138 days, enabling sequential and controlled release of payloads. Based on this, a MG\u2010709 double\u2010layered formulation which co\u2010delivered cancer cell membrane\u2010coated nanoparticle\/siRNA complex (siStat3@CMP) in the outer layer, and DC membrane\u2010coated nanoparticle\/cancer cell lysate complex (DMLD) in the inner layer. The results demonstrated that siStat3@CMP was released first and exerted its apoptosis\u2010inducing effect, resulting in the release of tumor\u2010associated antigens (TAAs). Subsequently, TAAs as well as immune cells migrated into the inner layer, where they worked together with DMLD to ignite immune responses. The activated immune cells were then released to perform immunotherapeutic effects. Facilitated by this mechanism, in situ implantation of the MG\u2010709 scaffold efficiently suppressed the development of multiple colorectal cancer models. The study provides a new solution for the collaboration of CMNPs in tumor immunogene therapy.<\/jats:p>","DOI":"10.1002\/smll.75388","type":"journal-article","created":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T09:14:27Z","timestamp":1787390067000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Efficient Colon Cancer Immunogene Therapy by Hydrogel Ball Loaded With Two Types of Cell Membrane\u2010Coated Nanoparticles"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2277-531X","authenticated-orcid":false,"given":"Jingmei","family":"Li","sequence":"first","affiliation":[{"name":"Department of Biotherapy Cancer Center and State Key Laboratory of Biotherapy West China Hospital Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Biotherapy Cancer Center and State Key Laboratory of Biotherapy West China Hospital Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-6013-5801","authenticated-orcid":false,"given":"Xiayu","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Biotherapy Cancer Center and State Key Laboratory of Biotherapy West China Hospital Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3301-2238","authenticated-orcid":false,"given":"Shan","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Biotherapy Cancer Center and State Key Laboratory of Biotherapy West China Hospital Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jieping","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Biotherapy Cancer Center and State Key Laboratory of Biotherapy West China Hospital Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xizi","family":"Fu","sequence":"additional","affiliation":[{"name":"Department of Biotherapy Cancer Center and State Key Laboratory of Biotherapy West China Hospital Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Biotherapy Cancer Center and State Key Laboratory of Biotherapy West China Hospital Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lixia","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Personalized Drug Therapy Key Laboratory of Sichuan Province Sichuan Academy of Medical Sciences &amp; Sichuan Provincial People's Hospital School of Medicine University of Electronic Science and Technology of China  Chengdu China"},{"name":"Department of Neurology Sichuan Provincial People's Hospital University of Electronic Science and Technology of China  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingmei","family":"Duan","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Personalized Drug Therapy Key Laboratory of Sichuan Province Sichuan Academy of Medical Sciences &amp; Sichuan Provincial People's Hospital School of Medicine University of Electronic Science and Technology of China  Chengdu China"},{"name":"Department of Neurology Sichuan Provincial People's Hospital University of Electronic Science and Technology of China  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke","family":"Men","sequence":"additional","affiliation":[{"name":"Department of Biotherapy Cancer Center and State Key Laboratory of Biotherapy West China Hospital Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,22]]},"reference":[{"issue":"3","key":"e_1_2_8_2_1","first-page":"229","article-title":"Global Cancer Statistics 2022: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"74","author":"Bray F.","year":"2024","journal-title":"CA: A Cancer Journal for Clinicians"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12672\u2010025\u201002198\u20108"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12943\u2010020\u201001258\u20107"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.18632\/aging.205847"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008\u20105472.can\u201010\u20104660"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1136\/jitc\u20102024\u2010010612"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2025.113764"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.matt.2024.10.017"},{"issue":"5","key":"e_1_2_8_10_1","doi-asserted-by":"crossref","DOI":"10.1002\/smtd.202201412","article-title":"Biomimetic Active Materials Guided Immunogenic Cell Death for Enhanced Cancer Immunotherapy","volume":"7","author":"Huang G.","year":"2023","journal-title":"Small Methods"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40820\u2010019\u20100330\u20109"},{"issue":"23","key":"e_1_2_8_12_1","doi-asserted-by":"crossref","DOI":"10.1002\/adma.201706759","article-title":"Cell Membrane Coating Nanotechnology","volume":"30","author":"Fang R. 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