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Nevertheless, being replication\u2010competent pathogens, they may induce adverse effects in cancer patients who have compromised immune systems. Here, the results show that the 4\u2010hydroxytamoxifen (4\u2010HT)\u2010dependent H1N1 influenza virus S218 can inhibit the proliferation and lung metastasis of melanoma in vivo, and 4\u2010HT enhances the anti\u2010tumor effect of S218 virus. To activate the S218 virus in the tumors, tumor\u2010targeted nanostructured lipid carriers (NLCs) modified with folate (FA) are developed to encapsulate 4\u2010HT. This approach improves the tumor\u2010targeting capability and anti\u2010tumor immunity of the S218 virus. Furthermore, the combination of the S218 virus with the small molecule STING agonist SR717 further enhances the regression of lung metastases. The findings demonstrate a novel oncolytic strategy utilizing nanocarriers to deliver small\u2010molecule drugs for activating viruses in the tumors, offering insights for oncolytic virus development.<\/jats:p>","DOI":"10.1002\/adhm.202502017","type":"journal-article","created":{"date-parts":[[2025,8,29]],"date-time":"2025-08-29T11:26:51Z","timestamp":1756466811000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Selective Activation of Conditionally Replicating Influenza A Virus in Pulmonary Tumors for Enhanced Oncolytic Efficacy and Systemic Safety"],"prefix":"10.1002","volume":"15","author":[{"given":"Ji","family":"Chen","sequence":"first","affiliation":[{"name":"School of Pharmacy Qingdao University  Qingdao 266021 China"},{"name":"Department of Pharmacy The Affiliated Hospital of Guizhou Medical University  Guiyang 550000 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