{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T16:03:31Z","timestamp":1789488211541,"version":"build-2803163510"},"reference-count":29,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,1,18]],"date-time":"2026-01-18T00:00:00Z","timestamp":1768694400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,18]],"date-time":"2026-01-18T00:00:00Z","timestamp":1768694400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["aiche.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Bioengineering &amp;amp; Transla Med"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Hepatocellular carcinoma (HCC) is a major cause of cancer\u2010related deaths. Advanced\u2010stage patients face poor prognosis due to chemotherapy resistance and an immunosuppressive tumor microenvironment (TME). Cellular senescence, marked by the senescence\u2010associated secretory phenotype, promotes tumor progression and immune evasion. Although honokiol (HKL) shows strong antitumor activity, its clinical use is limited by poor solubility, rapid clearance, and low bioavailability. Here, we report HKL\u2010loaded poly(ethylene glycol)\u2010poly(\u03b5\u2010caprolactone)\u2010poly(ethylene glycol) triblock copolymer nanomicelles (HKL\u2010nm) as a multifunctional nanotherapeutic platform. HKL\u2010nm exhibited a uniform spherical shape with a diameter of 60.93\u2009\u00b1\u20095.7\u2009nm, near\u2010neutral charge (\u22120.28\u2009\u00b1\u20090.1\u2009mV), and high encapsulation efficiency (85.9\u2009\u00b1\u20094.9%). It enabled sustained drug release (70.04\u2009\u00b1\u20096.2% over 200\u2009h) and significantly improved oral pharmacokinetics (area under the curve increased 6.26\u2010fold and\n                    <jats:italic>C<\/jats:italic>\n                    <jats:sub>max<\/jats:sub>\n                    increased 4.06\u2010fold). Specifically, the HKL drug concentration at the tumor site was enhanced by 3.52\u2010fold. Mechanistically, HKL\u2010nm suppressed senescence markers (p53, p16, and p21) and senescence\u2010associated \u03b2\u2010galactosidase positivity via a Sirtuin 3\u2010dependent pathway, inhibiting cytoplasmic mitochondrial DNA leakage and cGAS\u2010STING signaling. In Hepa1\u20106 cells xenografts, combination therapy with HKL\u2010nm and the senolytic cocktail dasatinib\u2009+\u2009quercetin achieved tumor volume reduction, with transcriptomic analysis validating enrichment of immune activation pathways. This was accompanied by enhanced infiltration of CD8\n                    <jats:sup>+<\/jats:sup>\n                    cytotoxic T cells and mature dendritic cells, coupled with profound suppression of myeloid\u2010derived suppressor cells. By integrating nanodelivery, senescence modulation, and immuno\u2010oncology, HKL\u2010nm represents a promising strategy to overcome therapeutic resistance in HCC, providing a preclinical basis for translation to solid tumors.\n                  <\/jats:p>","DOI":"10.1002\/btm2.70111","type":"journal-article","created":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T07:38:12Z","timestamp":1768808292000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Honokiol\u2010loaded nanomicelles reprogram senescence and immune evasion in hepatocellular carcinoma via\n                    <scp>SIRT3<\/scp>\n                    \u2010mediated mitochondrial stabilization"],"prefix":"10.1002","volume":"11","author":[{"given":"Wenxing","family":"Deng","sequence":"first","affiliation":[{"name":"Department of Hepatobiliary and Pancreatic Surgery, The Central Hospital of Wuhan, Tongji Medical College Huazhong University of Science and Technology  Wuhan Hubei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yizhi","family":"Wu","sequence":"additional","affiliation":[{"name":"Department and Institute of Infectious Disease, Tongji Hospital, Tongji Medical College Huazhong University of Science and Technology  Wuhan Hubei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yisheng","family":"Yin","sequence":"additional","affiliation":[{"name":"Department of Urology, Tongji Hospital, Tongji Medical College Huazhong University of Science and Technology  Wuhan Hubei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-5740-9485","authenticated-orcid":false,"given":"Jing","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College Huazhong University of Science and Technology, Key Laboratory of Organ Transplantation, Ministry of Education, NHC Key Laboratory of Organ Transplantation, Key Laboratory of Organ Transplantation, Chinese Academy of Medical Sciences, Organ Transplantation Clinical Medical Research Center of Hubei Province  Wuhan Hubei China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,1,18]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2023.03.017"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/ot9.0000000000000123"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/HEP.0000000000000237"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-025-02284-z"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jare.2024.04.007"},{"key":"e_1_2_11_7_1","article-title":"Cellular senescence in liver cancer: how dying cells become \u201czombie\u201d enemies","volume":"12","author":"Gazzillo 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