{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T08:47:45Z","timestamp":1791967665440,"version":"4.3.4"},"reference-count":50,"publisher":"American Association for the Advancement of Science (AAAS)","funder":[{"DOI":"10.13039\/501100007129","name":"Natural Science Foundation of Shandong Province","doi-asserted-by":"publisher","award":["ZR2025MS1390"],"award-info":[{"award-number":["ZR2025MS1390"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Traditional Chinese Medicine Science and Technology Program of Shandong Province","award":["Q2023002"],"award-info":[{"award-number":["Q2023002"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82202836"],"award-info":[{"award-number":["82202836"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Shandong Province Medical and Health Technology Development Plan Project","award":["202511001272"],"award-info":[{"award-number":["202511001272"]}]}],"content-domain":{"domain":["spj.science.org"],"crossmark-restriction":true},"short-container-title":["Biomater Res"],"published-print":{"date-parts":[[2026,1,1]]},"abstract":"<jats:p>Hepatocellular carcinoma (HCC) exhibits profound metabolic reprogramming, particularly enhanced glycolytic activity, which represents a therapeutic vulnerability. However, the remarkable adaptability of HCC metabolism allows tumor cells to compensate for metabolic disturbances and preserve cellular homeostasis, reducing the effectiveness of metabolism-targeted strategies. Therefore, strategies sustaining metabolic perturbation beyond tumor adaptive capacity are needed. Herein, we developed a pH-responsive zwitterion-modified core\u2013shell tecto dendrimer nanocarrier (CSTD-PS) for resveratrol (Res) delivery to overcome these limitations and potentiate HCC therapy. CSTD-PS was constructed through dynamic boronate ester-mediated assembly and zwitterionic surface modification, enabling Res encapsulation and pH-responsive release. After Res encapsulation, Res@CSTD-PS exhibited enhanced cellular uptake and nanocarrier-associated tumor localization, resulting in superior antitumor efficacy in HCC models compared with free Res. Mechanistically, Res@CSTD-PS suppressed glycolytic regulators, including hexokinase 2, glucose transporter 1, and pyruvate kinase M2, accompanied by enhanced stress responses (glucose-regulated protein 78 and nuclear factor erythroid 2-related factor 2) and p53\/caspase-3-associated apoptotic signaling. Res@CSTD-PS also reduced programmed death-ligand 1 expression, suggesting potential attenuation of immune-evasive characteristics. Collectively, this study introduces a strategy enabled by intelligent dendrimer-based nanomedicine, providing a promising approach for enhancing natural compound-based therapy against HCC.<\/jats:p>","DOI":"10.34133\/bmr.0428","type":"journal-article","created":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T16:40:08Z","timestamp":1790786408000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark_01","source":"Crossref","is-referenced-by-count":0,"title":["Resveratrol-Loaded Responsive Core\u2013Shell Tecto Dendrimers Potentiate Hepatocellular Carcinoma Therapy"],"prefix":"10.34133","volume":"30","author":[{"given":"Wenchao","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Clinical Laboratory, Shandong Cancer Hospital and Institute, \rShandong First Medical University &amp; Shandong Academy of Medical Sciences, Jinan 250117, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junjie","family":"Liu","sequence":"additional","affiliation":[{"name":"DWI-Leibniz-Institute for Interactive Materials, Institute for Technical and Macromolecular Chemistry, \rRWTH Aachen University, Aachen 52074, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenze","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Shandong Cancer Hospital and Institute, \rShandong First Medical University &amp; Shandong Academy of Medical Sciences, Jinan 250117, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-9258-8169","authenticated-orcid":false,"given":"Wenqing","family":"Man","sequence":"additional","affiliation":[{"name":"Medical Science and Technology Innovation Center, \rShandong First Medical University &amp; Shandong Academy of Medical Sciences, Jinan 250117, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Medical Science and Technology Innovation Center, \rShandong First Medical University &amp; Shandong Academy of Medical Sciences, Jinan 250117, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyi","family":"Zheng","sequence":"additional","affiliation":[{"name":"Medical Science and Technology Innovation Center, \rShandong First Medical University &amp; Shandong Academy of Medical Sciences, Jinan 250117, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yupeng","family":"Wang","sequence":"additional","affiliation":[{"name":"Biomedical Sciences College &amp; Shandong Medical Biotechnology Research Center, National Health Commission Key Laboratory of Biotechnology Drugs, \rShandong First Medical University &amp; Shandong Academy of Medical Sciences, Jinan 250117, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yao","family":"Shi","sequence":"additional","affiliation":[{"name":"Biomedical Sciences College &amp; Shandong Medical Biotechnology Research Center, National Health Commission Key Laboratory of Biotechnology Drugs, \rShandong First Medical University &amp; Shandong Academy of Medical Sciences, Jinan 250117, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinghai","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Shandong Cancer Hospital and Institute, \rShandong First Medical University &amp; Shandong Academy of Medical Sciences, Jinan 250117, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1125-1089","authenticated-orcid":true,"given":"Cong","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Shandong Cancer Hospital and Institute, \rShandong First Medical University &amp; Shandong Academy of Medical Sciences, Jinan 250117, China."},{"name":"Medical Science and Technology Innovation Center, \rShandong First Medical University &amp; Shandong Academy of Medical Sciences, Jinan 250117, China."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","published-online":{"date-parts":[[2026,10,14]]},"reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-023-00818-8"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41571-023-00825-3"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(22)01200-4"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2021.11.018"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1915745"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-022-00704-9"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13215524"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41571-021-00573-2"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/s12276-025-01415-2"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-020-00240-3"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2015.12.001"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.1600200"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-21-1059"},{"issue":"1","key":"e_1_3_4_15_2","first-page":"126","article-title":"Emerging roles and the regulation of aerobic glycolysis in hepatocellular carcinoma","volume":"39","author":"Feng J","year":"2020","unstructured":"Feng J, Li J, Wu L, Yu Q, Ji J, Wu J, Dai W, Guo C. Emerging roles and the regulation of aerobic glycolysis in hepatocellular carcinoma. J Hepatol. 2020;39(1):126.","journal-title":"J Hepatol"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-026-02578-w"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaw5473"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrc.2017.53"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2021.05.001"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms18122589"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1080\/10408398.2022.2101428"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms232213689"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.3390\/biom16010118"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.3390\/cimb47121006"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41698-017-0038-6"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.carbpol.2026.125526"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-020-0090-8"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/natrevmats.2016.14"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.2147\/IJN.S443692"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1039\/C9NR08309J"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1521-4095(200006)12:11<796::AID-ADMA796>3.0.CO;2-1"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.progpolymsci.2005.01.007"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.bioconjchem.1c00005"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1039\/B901839P"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2020.213463"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1002\/marc.202400251"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1039\/C7TB02585H"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1039\/D0TB00346H"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2023.05.021"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.biomac.1c00262"},{"key":"e_1_3_4_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nantod.2021.101325"},{"key":"e_1_3_4_42_2","doi-asserted-by":"publisher","DOI":"10.1039\/D3BM00375B"},{"key":"e_1_3_4_43_2","doi-asserted-by":"publisher","DOI":"10.1111\/cpr.13346"},{"key":"e_1_3_4_44_2","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13020188"},{"key":"e_1_3_4_45_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2017.06.017"},{"key":"e_1_3_4_46_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2020.06.001"},{"key":"e_1_3_4_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.08.016"},{"key":"e_1_3_4_48_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41571-019-0203-7"},{"key":"e_1_3_4_49_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2019.03.068"},{"key":"e_1_3_4_50_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2025.115804"},{"key":"e_1_3_4_51_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41420-024-02110-3"}],"container-title":["Biomaterials Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/spj.science.org\/doi\/pdf\/10.34133\/bmr.0428","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T08:00:50Z","timestamp":1791964850000},"score":1,"resource":{"primary":{"URL":"https:\/\/spj.science.org\/doi\/10.34133\/bmr.0428"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,1]]},"references-count":50,"alternative-id":["10.34133\/bmr.0428"],"URL":"https:\/\/doi.org\/10.34133\/bmr.0428","relation":{},"ISSN":["2055-7124"],"issn-type":[{"value":"2055-7124","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,1]]},"assertion":[{"value":"2026-08-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-18","order":1,"name":"revised","label":"Revised","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-25","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-14","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"0428"}}