{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T13:14:56Z","timestamp":1776258896463,"version":"3.50.1"},"reference-count":28,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T00:00:00Z","timestamp":1774828800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Conventional (cTACE) and drug-eluting bead transarterial chemoembolization (D-TACE) are limited by physicochemical incompatibility when lipiodol and microspheres are mixed. This study evaluated a sequential co-delivery strategy (M-TACE) designed to synergize these agents in a rabbit VX2 liver tumor model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Animals were randomized into control, cTACE, D-TACE, and M-TACE (epirubicin-lipiodol emulsion followed by epirubicin-loaded microspheres) groups. Primary outcomes included pharmacokinetics, tumor necrosis, and lipiodol distribution.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The cTACE group showed a higher systemic peak epirubicin concentration (C \u223c max\u223c: 276.08 \u00b1 41.74\u00a0ng\/mL) than D-TACE (79.37 \u00b1 16.26\u00a0ng\/mL) and M-TACE (92.13 \u00b1 12.68\u00a0ng\/mL) (p &amp;lt; 0.001), while total 24-h exposure (AUC0\u201324\u00a0h) was comparable. M-TACE achieved intratumoral drug concentrations equivalent to D-TACE at day 1 and 14, confirming unimpaired microsphere elution. M-TACE induced superior tumor necrosis (95.4% \u00b1 6.7%) versus cTACE (85.1% \u00b1 6.2%) and D-TACE (88.6% \u00b1 8.4%) (p &amp;lt; 0.001), with less peritumoral liver necrosis than D-TACE (50.9% \u00b1 6.0% vs. 61.7% \u00b1 9.0%, p = 0.039). M-TACE also yielded more focal lipiodol deposition (72.2% \u00b1 7.4% tumor coverage) with reduced parenchymal extravasation versus cTACE (92.9% \u00b1 7.8%; p &amp;lt; 0.001).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The sequential M-TACE strategy successfully decouples lipiodol and microsphere delivery, circumvents the practical consequences of incompatibility while harnessing synergistic advantages\u2014lipiodol\u2019s capillary blockade and microspheres\u2019 sustained drug release\u2014resulting in enhanced efficacy and favorable local safety profile.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1800481","type":"journal-article","created":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T05:27:19Z","timestamp":1774848439000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Sequential and synergistic delivery of lipiodol and drug-eluting microspheres circumvents incompatibility to enhance targeted chemoembolization"],"prefix":"10.3389","volume":"17","author":[{"given":"Nan","family":"Du","sequence":"first","affiliation":[{"name":"Department of Interventional Radiology, Fudan University Shanghai Cancer Center","place":["Shanghai, China"]},{"name":"Department of Oncology, Shanghai Medical College, Fudan University","place":["Shanghai, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wen","family":"Zhang","sequence":"additional","affiliation":[{"name":"Zhongshan Hospital Fudan University","place":["Shanghai, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chao","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Interventional Radiology, Fudan University Shanghai Cancer Center","place":["Shanghai, China"]},{"name":"Department of Oncology, Shanghai Medical College, Fudan University","place":["Shanghai, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Interventional Radiology, Fudan University Shanghai Cancer Center","place":["Shanghai, China"]},{"name":"Department of Oncology, Shanghai Medical College, Fudan University","place":["Shanghai, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinhong","family":"He","sequence":"additional","affiliation":[{"name":"Department of Interventional Radiology, Fudan University Shanghai Cancer Center","place":["Shanghai, China"]},{"name":"Department of Oncology, Shanghai Medical College, Fudan University","place":["Shanghai, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianjun","family":"Luo","sequence":"additional","affiliation":[{"name":"Zhongshan Hospital Fudan University","place":["Shanghai, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhiping","family":"Yan","sequence":"additional","affiliation":[{"name":"Zhongshan Hospital Fudan University","place":["Shanghai, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wen-Tao","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Interventional Radiology, Fudan University Shanghai Cancer Center","place":["Shanghai, China"]},{"name":"Department of Oncology, Shanghai Medical College, Fudan University","place":["Shanghai, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,30]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"5626","DOI":"10.7150\/thno.34778","article-title":"Evaluation of novel formulations for transarterial chemoembolization: combining elements of lipiodol emulsions with drug-eluting beads","volume":"9","author":"Caine","year":"2019","journal-title":"Theranostics"},{"key":"B2","doi-asserted-by":"publisher","first-page":"645","DOI":"10.2214\/AJR.15.14758","article-title":"Conventional ethiodized oil transarterial chemoembolization for treatment of hepatocellular carcinoma: contemporary single-center review of clinical outcomes","volume":"206","author":"Casadaban","year":"2016","journal-title":"AJR Am. 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