{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T12:46:24Z","timestamp":1791377184373,"version":"4.3.2"},"reference-count":31,"publisher":"Wiley","issue":"22","license":[{"start":{"date-parts":[[2023,5,28]],"date-time":"2023-05-28T00:00:00Z","timestamp":1685232000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["21838002"],"award-info":[{"award-number":["21838002"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Adv Healthcare Materials"],"published-print":{"date-parts":[[2023,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>By conjugating a chemotherapeutic candidate drug 4<jats:italic>\u03b2<\/jats:italic>\u2010NH\u2010(5\u2010aminoindazole)\u2010podophyllotoxin (<jats:italic>\u03b2<\/jats:italic>IZP) and an immunosuppressive protein galectin\u20101 targeted aptamer AP74, a chemo\u2010immunotherapy molecule (AP74\u2010<jats:italic>\u03b2<\/jats:italic>IZP) is developed against liver cancer. AP74\u2010<jats:italic>\u03b2<\/jats:italic>IZP can target galectin\u20101 and enrich the tumor microenvironment to improve the tumor inhibition ratio by 6.3%, higher than that of <jats:italic>\u03b2<\/jats:italic>IZP in a HepG2 xenograft model. In safety evaluation, <jats:italic>\u03b2<\/jats:italic>IZP cannot be released from AP74\u2010<jats:italic>\u03b2<\/jats:italic>IZP in normal tissues with low glutathione level. Therefore, the degrees of organs injury and myelosuppression after the treatment with AP74\u2010<jats:italic>\u03b2<\/jats:italic>IZP are lower than those with <jats:italic>\u03b2<\/jats:italic>IZP. After 21 d treatment at a drug dose of 5\u00a0mg kg<jats:sup>\u22121<\/jats:sup>, AP74\u2010<jats:italic>\u03b2<\/jats:italic>IZP does not cause\u00a0weight loss in mice, while the weight is significantly reduced by 24% and 14% from oxaliplatin and <jats:italic>\u03b2<\/jats:italic>IZP, respectively. In immune synergy, AP74\u2010IZP enhances CD4\/CD8 cell infiltration to promote the expression of cell factor (i.e., IL\u20102, TNF\u2010<jats:italic>\u03b1<\/jats:italic>, and IFN\u2010<jats:italic>\u03b3<\/jats:italic>), which further improves the antitumor activity. The tumor inhibition ratio of AP74\u2010<jats:italic>\u03b2<\/jats:italic>IZP is 70.2%, which is higher than that of AP74 (35.2%) and <jats:italic>\u03b2<\/jats:italic>IZP (48.8%). Because of the dual effects of chemotherapy and immunotherapy, AP74\u2010<jats:italic>\u03b2<\/jats:italic>IZP exhibits superior activity and lower toxicity. The approach developed in this work could be applicable to other chemotherapy drugs.<\/jats:p>","DOI":"10.1002\/adhm.202203144","type":"journal-article","created":{"date-parts":[[2023,5,4]],"date-time":"2023-05-04T13:45:23Z","timestamp":1683207923000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Conjugating 4<i>\u03b2<\/i>\u2010NH\u2010(5\u2010Aminoindazole)\u2010podophyllotoxin and Galectin\u20101\u2010Targeted Aptamer for Synergistic Chemo\u2010Immunotherapy of Hepatocellular Carcinoma"],"prefix":"10.1002","volume":"12","author":[{"given":"Ying","family":"Cong","sequence":"first","affiliation":[{"name":"State Key Laboratory of Microbial Technology Shandong University  Qingdao 266237 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shu\u2010Yue","family":"Zhang","sequence":"additional","affiliation":[{"name":"China International Science and Technology Cooperation Base of Food Nutrition\/Safety and Medicinal Chemistry College of Biotechnology Tianjin University of Science &amp; Technology  Tianjin 300457 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula Yun\u2010Zhi","family":"Tang","sequence":"additional","affiliation":[{"name":"Jinan Zhensheng School  Jinan 250102 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong\u2010Mei","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Microbial Technology Shandong University  Qingdao 266237 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue","family":"Liu","sequence":"additional","affiliation":[{"name":"Jinan Food and Drug Inspection and Testing Center  Jinan 250101 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Zhao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Microbial Technology Shandong University  Qingdao 266237 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