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However, HCC is characterized by a poor prognosis and high recurrence rates (\u224830%), partly due to a hypoxic pro\u2010angiogenic and pro\u2010cancerous microenvironment. This study investigates how modifying tissue stress while improving drug exposure in target organs may maximize the therapeutic outcomes. Porous degradable polymeric microspheres (MS) are designed to obtain a gradual occlusion of the hepatic artery that nourishes the liver, while enabling efficient drug perfusion to the tumor site. The fabricated porous MS are introduced intrahepatically and designed to release a combination therapy of Doxorubicin (DOX) and Tirapazamine (TPZ), which is a hypoxia\u2010activated prodrug. Liver cancer cell lines that are treated with the combination therapy under hypoxia reveal a synergic anti\u2010proliferation effect. An orthotopic liver cancer model, based on N1\u2010S1 hepatoma in rats, is used for the efficacy, biodistribution, and safety studies. Porous DOX\u2010TPZ MS are very effective in suppressing tumor growth in rats, and induction tissue necrosis is associated with high intratumor drug concentrations. Porous particles without drugs show some advantages over nonporous particles, suggesting that morphology may affect the treatment outcomes.<\/jats:p>","DOI":"10.1002\/adhm.202301548","type":"journal-article","created":{"date-parts":[[2023,6,14]],"date-time":"2023-06-14T20:21:05Z","timestamp":1686774065000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Drug\u2010Eluting Porous Embolic Microspheres for Trans\u2010Arterial Delivery of Dual Synergistic Anticancer Therapy for the Treatment of Liver Cancer"],"prefix":"10.1002","volume":"12","author":[{"given":"Benzion","family":"Amoyav","sequence":"first","affiliation":[{"name":"The Institute for Drug Research School of Pharmacy The Faculty of Medicine The Hebrew University of Jerusalem Jerusalem 91120 Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allan I.","family":"Bloom","sequence":"additional","affiliation":[{"name":"Department of Medical Imaging\u2010Interventional Radiology Hadassah Medical Center Jerusalem 911200 Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoel","family":"Goldstein","sequence":"additional","affiliation":[{"name":"The Institute for Drug Research School of Pharmacy The Faculty of Medicine The Hebrew University of Jerusalem Jerusalem 91120 Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafael","family":"Miller","sequence":"additional","affiliation":[{"name":"Department of General Surgery Kaplan Medical Center Affiliated to Hebrew University Jerusalem Rehovot 76100 Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariana","family":"Sharam","sequence":"additional","affiliation":[{"name":"Authority for Biological and Biomedical Models Hadassah Medical Center  Jerusalem 911200 Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnon","family":"Fluksman","sequence":"additional","affiliation":[{"name":"The Institute for Drug Research School of Pharmacy The Faculty of Medicine The Hebrew University of Jerusalem Jerusalem 91120 Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2468-5978","authenticated-orcid":false,"given":"Ofra","family":"Benny","sequence":"additional","affiliation":[{"name":"The Institute for Drug Research School of Pharmacy The Faculty of Medicine The Hebrew University of Jerusalem Jerusalem 91120 Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,6,26]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.2147\/HP.S93413"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13046-019-1487-2"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers14112798"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1200\/JOP.2017.022996"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/jgh.15169"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v20.i3.745"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/jfb8020012"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00270-009-9762-9"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1159\/000502774"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jvir.2007.02.031"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1080\/10717544.2021.1938756"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-00709-4"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsami.7b14330"},{"key":"e_1_2_9_14_1","first-page":"554","volume":"2209413","author":"Zhu X.","year":"2023","journal-title":"Adv. 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