{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T04:22:24Z","timestamp":1777436544371,"version":"3.51.4"},"reference-count":30,"publisher":"Wiley","issue":"22","license":[{"start":{"date-parts":[[2025,6,17]],"date-time":"2025-06-17T00:00:00Z","timestamp":1750118400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000147","name":"Canadian Cancer Society","doi-asserted-by":"publisher","award":["706231"],"award-info":[{"award-number":["706231"]}],"id":[{"id":"10.13039\/501100000147","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["PJT\u2010168861"],"award-info":[{"award-number":["PJT\u2010168861"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004489","name":"Mitacs","doi-asserted-by":"publisher","award":["IT39623"],"award-info":[{"award-number":["IT39623"]}],"id":[{"id":"10.13039\/501100004489","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004489","name":"Mitacs","doi-asserted-by":"publisher","award":["IT39521"],"award-info":[{"award-number":["IT39521"]}],"id":[{"id":"10.13039\/501100004489","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Adv Healthcare Materials"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Liver cancers are often diagnosed at advanced stages and are the fourth leading cause of cancer death globally. Liver metastases, particularly from colorectal cancer, occur in 66% of patients. Immunotherapies for these cancers are limited by immunosuppressive tumor microenvironments. To address this, phospholipid\u2010free small unilamellar vesicles (PFSUV) are developed to deliver the toll\u2010like receptor 7 agonist Imiquimod (IMQ) to hepatocytes. PFSUV consists of 83 mol% cholesterol and 17 mol% Tween80, with IMQ encapsulated in these 75\u2010nm particles. Intravenous administration of PFSUV\u2010IMQ sustained liver IFN\u2010\n                    <jats:italic>\u03b1<\/jats:italic>\n                    levels over 24 h while reducing systemic exposure. In a CT26 liver metastasis model, PFSUV\u2010IMQ combined with Oxaliplatin reduced tumor size, increased CD8+ T cell infiltration, and enhanced tumor apoptosis. In an HCA\u20101 liver cancer model, the same treatment decreased tumor burden, increased apoptosis, and reduced lung metastases. Flow cytometry revealed increased CD86+\/MHC\u2010II+ dendritic cells and IFN\u2010\n                    <jats:italic>\u03b3<\/jats:italic>\n                    + CD8+ T cells in treated tumors. RNA\u2010seq shows enrichment of innate immune activation genes after a single dose. These findings suggest that targeted IMQ delivery activates the tumor immune microenvironment, leading to reduced tumor burden in liver cancer and metastasis models.\n                  <\/jats:p>","DOI":"10.1002\/adhm.202501691","type":"journal-article","created":{"date-parts":[[2025,6,17]],"date-time":"2025-06-17T07:39:01Z","timestamp":1750145941000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Imiquimod\u2010Loaded Phospholipid\u2010Free Small Unilamellar Vesicles Activate the Tumor Immune Microenvironment to Treat Liver Cancer and Liver Metastases"],"prefix":"10.1002","volume":"14","author":[{"given":"Vanessa","family":"Chan","sequence":"first","affiliation":[{"name":"Faculty of Pharmaceutical Sciences University of British Columbia  Vancouver BC V6T 1Z3 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Medicine China Medical University  Taichung Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisa","family":"Pfeifer","sequence":"additional","affiliation":[{"name":"Faculty of Pharmaceutical Sciences University of British Columbia  Vancouver BC V6T 1Z3 Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luke","family":"Rushton","sequence":"additional","affiliation":[{"name":"Faculty of Pharmaceutical Sciences University of British Columbia  Vancouver BC V6T 1Z3 Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Po\u2010Han","family":"Chao","sequence":"additional","affiliation":[{"name":"Faculty of Pharmaceutical Sciences University of British Columbia  Vancouver BC V6T 1Z3 Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Feng","family":"Zhao","sequence":"additional","affiliation":[{"name":"Faculty of Pharmaceutical Sciences University of British Columbia  Vancouver BC V6T 1Z3 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