{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T04:18:53Z","timestamp":1788322733542,"version":"build-2803163510"},"reference-count":57,"publisher":"Wiley","issue":"36","license":[{"start":{"date-parts":[[2024,7,18]],"date-time":"2024-07-18T00:00:00Z","timestamp":1721260800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004608","name":"Natural Science Foundation of Jiangsu Province","doi-asserted-by":"publisher","award":["BK20230165"],"award-info":[{"award-number":["BK20230165"]}],"id":[{"id":"10.13039\/501100004608","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004608","name":"Natural Science Foundation of Jiangsu Province","doi-asserted-by":"publisher","award":["BE2023695"],"award-info":[{"award-number":["BE2023695"]}],"id":[{"id":"10.13039\/501100004608","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004608","name":"Natural Science Foundation of Jiangsu Province","doi-asserted-by":"publisher","award":["BK20231136"],"award-info":[{"award-number":["BK20231136"]}],"id":[{"id":"10.13039\/501100004608","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2023M731634"],"award-info":[{"award-number":["2023M731634"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82303774"],"award-info":[{"award-number":["82303774"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82130106"],"award-info":[{"award-number":["82130106"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32250016"],"award-info":[{"award-number":["32250016"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Materials"],"published-print":{"date-parts":[[2024,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Lung metastases are the leading cause of death among cancer patients. The challenges of inefficient drug delivery, compounded by a robust immunosuppressive microenvironment, make effective treatment difficult. Here, an innovative dual\u2010engineered macrophage\u2010microbe encapsulation (Du\u2010EMME) therapy is developed that integrates modified macrophages and engineered antitumor bacteria. These engineered macrophages, termed R\u2010GEM cells, are designed to express RGD peptides on extracellular membranes, enhancing their tumor cell binding and intratumor enrichment. R\u2010GEM cells are cocultured with attenuated <jats:italic>Salmonella typhimurium<\/jats:italic> VNP20009, producing macrophage\u2010microbe encapsulation (R\u2010GEM\/VNP cells). The intracellular bacteria maintain bioactivity for more than 24\u00a0h, and the bacteria released from R\u2010GEM\/VNP cells within the tumor continue to exert bacteria\u2010mediated antitumor effects. This is further supported by macrophage\u2010based chemotaxis and camouflage, which enhance the intratumoral enrichment and biocompatibility of the bacteria. Additionally, R\u2010GEM cells loaded with IFN\u03b3\u2010secreting strains (VNP\u2010IFN\u03b3) form R\u2010GEM\/VNP\u2010IFN\u03b3 cells. Treatment with these cells effectively halts lung metastatic tumor progression in three mouse models (breast cancer, melanoma, and colorectal cancer). R\u2010GEM\/VNP\u2010IFN\u03b3 cells vigorously activate the tumor microenvironment, suppressing tumor\u2010promoting M2\u2010type macrophages, MDSCs, and Tregs, and enhancing tumor\u2010antagonizing M1\u2010type macrophages, mature DCs, and Teffs. Du\u2010EMME therapy offers a promising strategy for targeted and enhanced antitumor immunity in treating cancer metastases.<\/jats:p>","DOI":"10.1002\/adma.202406140","type":"journal-article","created":{"date-parts":[[2024,7,18]],"date-time":"2024-07-18T09:57:00Z","timestamp":1721296620000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Dual\u2010Engineered Macrophage\u2010Microbe Encapsulation for Metastasis Immunotherapy"],"prefix":"10.1002","volume":"36","author":[{"given":"Leyang","family":"Wu","sequence":"first","affiliation":[{"name":"The State Key Laboratory of Pharmaceutical Biotechnology and Department of Neurology of Nanjing Drum Tower Hospital School of Life Sciences and The Affiliated Hospital of Nanjing University Medical School Nanjing University Nanjing Jiangsu 210023 P. R. China"},{"name":"Nanjing Generecom Biotechnology Co., Ltd.  Nanjing Jiangsu 210023 P. R. China"},{"name":"Changzhou High\u2010Tech Research Institute of Nanjing University and Jiangsu TargetPharma Laboratories, Inc.  Changzhou Jiangsu 213164 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liyuan","family":"Qiao","sequence":"additional","affiliation":[{"name":"The State Key Laboratory of Pharmaceutical Biotechnology and Department of Neurology of Nanjing Drum Tower Hospital School of Life Sciences and The Affiliated Hospital of Nanjing University Medical School Nanjing University Nanjing Jiangsu 210023 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuhui","family":"Zhang","sequence":"additional","affiliation":[{"name":"The State Key Laboratory of Pharmaceutical Biotechnology and Department of Neurology of Nanjing Drum Tower Hospital School of Life Sciences and The Affiliated Hospital of Nanjing University Medical School Nanjing University Nanjing Jiangsu 210023 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiahui","family":"Qiu","sequence":"additional","affiliation":[{"name":"The State Key Laboratory of Pharmaceutical Biotechnology and Department of Neurology of Nanjing Drum Tower Hospital School of Life Sciences and The Affiliated Hospital of Nanjing University Medical School Nanjing University Nanjing Jiangsu 210023 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zengzheng","family":"Du","sequence":"additional","affiliation":[{"name":"The State Key Laboratory of Pharmaceutical Biotechnology and Department of Neurology of Nanjing Drum Tower Hospital School of Life Sciences and The Affiliated Hospital of Nanjing University Medical School Nanjing University Nanjing Jiangsu 210023 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Sun","sequence":"additional","affiliation":[{"name":"The State Key Laboratory of Pharmaceutical Biotechnology and Department of Neurology of Nanjing Drum Tower Hospital School of Life Sciences and The Affiliated Hospital of Nanjing University Medical School Nanjing University Nanjing Jiangsu 210023 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyao","family":"Chang","sequence":"additional","affiliation":[{"name":"The State Key Laboratory of Pharmaceutical Biotechnology and Department of Neurology of Nanjing Drum Tower Hospital School of Life Sciences and The Affiliated Hospital of Nanjing University Medical School Nanjing University Nanjing Jiangsu 210023 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Li","sequence":"additional","affiliation":[{"name":"The State Key Laboratory of Pharmaceutical Biotechnology and Department of Neurology of Nanjing Drum Tower Hospital School of Life Sciences and The Affiliated Hospital of Nanjing University Medical School Nanjing University Nanjing Jiangsu 210023 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenyang","family":"Li","sequence":"additional","affiliation":[{"name":"The State Key Laboratory of Pharmaceutical Biotechnology and Department of Neurology of Nanjing Drum Tower Hospital School of Life Sciences and The Affiliated Hospital of Nanjing University Medical School Nanjing University Nanjing Jiangsu 210023 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyue","family":"Qiao","sequence":"additional","affiliation":[{"name":"The State Key Laboratory of Pharmaceutical Biotechnology and Department of Neurology of Nanjing Drum Tower Hospital School of Life Sciences and The Affiliated Hospital of Nanjing University Medical School Nanjing University Nanjing Jiangsu 210023 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingpeng","family":"Yin","sequence":"additional","affiliation":[{"name":"The State Key Laboratory of Pharmaceutical Biotechnology and Department of Neurology of Nanjing Drum Tower Hospital School of Life Sciences and The Affiliated Hospital of Nanjing University Medical School Nanjing University Nanjing Jiangsu 210023 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7962-0402","authenticated-orcid":false,"given":"Zichun","family":"Hua","sequence":"additional","affiliation":[{"name":"The State Key Laboratory of Pharmaceutical Biotechnology and Department of Neurology of Nanjing Drum Tower Hospital School of Life Sciences and The Affiliated Hospital of Nanjing University Medical School Nanjing University Nanjing Jiangsu 210023 P. R. China"},{"name":"Nanjing Generecom Biotechnology Co., Ltd.  Nanjing Jiangsu 210023 P. R. China"},{"name":"Changzhou High\u2010Tech Research Institute of Nanjing University and Jiangsu TargetPharma Laboratories, Inc.  Changzhou Jiangsu 213164 P. R. China"},{"name":"Faculty of Pharmaceutical Sciences Xinxiang Medical University  Xinxiang Henan 453002 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,7,18]]},"reference":[{"key":"e_1_2_10_1_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-023-01725-9"},{"key":"e_1_2_10_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2023.03.003"},{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/adhm.202203356"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-023-01723-z"},{"key":"e_1_2_10_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2024.01.034"},{"key":"e_1_2_10_3_3","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-020-0462-y"},{"key":"e_1_2_10_3_4","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-019-0064-8"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.2c03573"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.201807211"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-023-01687-8"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2022.114136"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2022.114363"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.16135"},{"key":"e_1_2_10_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-023-01703-1"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.2013.206"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-04003-2"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-41768-8"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2021.06.004"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.2c07287"},{"key":"e_1_2_10_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41568-018-0070-z"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.apsb.2022.05.006"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.add9667"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2021.10.028"},{"key":"e_1_2_10_17_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202113649"},{"key":"e_1_2_10_17_3","doi-asserted-by":"publisher","DOI":"10.1002\/cam4.6800"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2020.07.043"},{"key":"e_1_2_10_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbcan.2012.12.007"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41551-023-01031-3"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202201042"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11427-021-1952-5"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2024.115204"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.2c08834"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1086\/315497"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aba8026"},{"key":"e_1_2_10_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/s44318-024-00076-7"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20151613"},{"key":"e_1_2_10_26_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.00898-07"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2015.01.039"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.01383"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0605200103"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/jam.15720"},{"key":"e_1_2_10_31_1","first-page":"701","volume":"4","author":"Mitchell G.","year":"2016","journal-title":"Microbiol. Spectr."},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.3390\/microorganisms8030407"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aba3546"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1349-7006.2009.01337.x"},{"key":"e_1_2_10_34_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms7673"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2002.20.1.142"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.17605"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-018-0029-z"},{"key":"e_1_2_10_37_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-22755-3"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-024-01765-9"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/adfm.202214842"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-023-01683-2"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mattod.2022.06.024"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpharm.2020.119177"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms232213735"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2021.110214"}],"updated-by":[{"DOI":"10.1002\/adma.202509778","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2025,6,17]],"date-time":"2025-06-17T00:00:00Z","timestamp":1750118400000}}],"container-title":["Advanced Materials"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/adma.202406140","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T19:54:36Z","timestamp":1759780476000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/adma.202406140"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,18]]},"references-count":57,"journal-issue":{"issue":"36","published-print":{"date-parts":[[2024,9]]}},"alternative-id":["10.1002\/adma.202406140"],"URL":"https:\/\/doi.org\/10.1002\/adma.202406140","archive":["Portico"],"relation":{"correction":[{"id-type":"doi","id":"10.1002\/adma.202509778","asserted-by":"object"}]},"ISSN":["0935-9648","1521-4095"],"issn-type":[{"value":"0935-9648","type":"print"},{"value":"1521-4095","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,18]]},"assertion":[{"value":"2024-04-29","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-07-18","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"2406140"}}