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Percutaneous intratumoral injection of anticancer agents has emerged as a potential alternative to systemic therapy to overcome tumor barriers, increase bioavailability, potentiate immunotherapy, and avoid systemic toxicity, which advanced\u2010stage cancer patients cannot tolerate. Here, an injectable OncoGel (OG) comprising of a nanocomposite hydrogel loaded with an ionic liquid (IL) is developed for achieving a predictable and uniform tumor ablation and long\u2010term slow release of anticancer agents into the ablation zone. Rigorous mechanical, physiochemical, drug release, cytotoxicity experiments, and ex vivo human tissue testing identify an injectable version of the OG with bactericidal properties against highly resistant bacteria. Intratumoral injection of OG loaded with Nivolumab (Nivo) and doxorubicin (Dox) into highly malignant tumor models in mice, rats, and rabbits demonstrates enhanced survival and tumor regression associated with robust tissue ablation and drug distribution throughout the tumor. Mass cytometry and proteomic studies in a mouse model of colorectal cancer that often metastasizes to the liver indicate an enhanced anticancer immune response following the intratumoral injection of OG. OG may augment immunotherapy and potentially improve outcomes in liver cancer patients.<\/jats:p>","DOI":"10.1002\/adma.202406080","type":"journal-article","created":{"date-parts":[[2024,8,15]],"date-time":"2024-08-15T23:56:07Z","timestamp":1723766167000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Percutaneous Delivery of Oncogel for Targeted Liver Tumor Ablation and Controlled Release of Therapeutics"],"prefix":"10.1002","volume":"36","author":[{"given":"Hassan","family":"Albadawi","sequence":"first","affiliation":[{"name":"Division of Vascular &amp; Interventional Radiology Laboratory for Patient Inspired Engineering Mayo Clinic  13400 East Shea Blvd. Scottsdale AR 85259 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zefu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Division of Vascular &amp; Interventional Radiology Laboratory for Patient Inspired Engineering Mayo Clinic  13400 East Shea Blvd. Scottsdale AR 85259 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyeongseop","family":"Keum","sequence":"additional","affiliation":[{"name":"Division of Vascular &amp; Interventional Radiology Laboratory for Patient Inspired Engineering Mayo Clinic  13400 East Shea Blvd. Scottsdale AR 85259 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enes","family":"Cevik","sequence":"additional","affiliation":[{"name":"Division of Vascular &amp; Interventional Radiology Laboratory for Patient Inspired Engineering Mayo Clinic  13400 East Shea Blvd. Scottsdale AR 85259 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bolni M","family":"Nagalo","sequence":"additional","affiliation":[{"name":"University of Arkansas for Medical Sciences College of Medicine Department of Pathology  301 West Markham Street Little Rock AR 72205 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seyda","family":"Gunduz","sequence":"additional","affiliation":[{"name":"Division of Vascular &amp; Interventional Radiology Laboratory for Patient Inspired Engineering Mayo Clinic  13400 East Shea Blvd. Scottsdale AR 85259 USA"},{"name":"Department of Medical Oncology Istinye University; Bahcesehir Liv Hospital  Istanbul 34517 Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirohito","family":"Kita","sequence":"additional","affiliation":[{"name":"Department of Immunology Division of Allergy, Asthma, and Clinical Immunology and the Department of Medicine Mayo Clinic Arizona  Scottsdale AR 85259 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4984-1778","authenticated-orcid":false,"given":"Rahmi","family":"Oklu","sequence":"additional","affiliation":[{"name":"Division of Vascular &amp; Interventional Radiology Laboratory for Patient Inspired Engineering Mayo Clinic  13400 East Shea Blvd. Scottsdale AR 85259 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,8,15]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1713263"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(22)01468-4"},{"key":"e_1_2_9_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2018.10.008"},{"key":"e_1_2_9_2_3","doi-asserted-by":"publisher","DOI":"10.1002\/hep.31558"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-019-0179-x"},{"key":"e_1_2_9_3_2","first-page":"280","volume":"6","author":"Spada F.","year":"2012","journal-title":"Ecancermedicalscience"},{"key":"e_1_2_9_3_3","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-018-0044-z"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1159\/000494843"},{"key":"e_1_2_9_5_1","first-page":"34","author":"Hu J. 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