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Sorafenib (SOR), a first-line targeted drug for advanced HCC treatment, has a battery of untoward side effects. Photothermal therapy (PTT) has been utilized as an effective adjuvant in synergy with other approaches. However, little is known about the tumoricidal efficacy of combining SOR with PTT for HCC. Herein, a novel versatile nanoparticle, Cu2\u2212xSe@SOR@PEG (CSP), that is based on a photothermal Cu2\u2212xSe core and SOR for simultaneously reinforcing PTT and reducing the adverse effects of SOR was constructed. The synthesized CSP exhibited a remarkably enhanced therapeutic effect upon 808 nm laser irradiation via dampening HCC cell propagation and metastasis and propelling cell apoptosis. The intravenous administration of CSP substantially suppressed tumor growth in a xenograft tumor mouse model. It was noted that the CSP manifested low toxicity and excellent biocompatibility. Together, this work indicates a promising and versatile tool that is based on synergistic PTT and molecular-targeted therapy for HCC management.<\/jats:p>","DOI":"10.3390\/nano12183191","type":"journal-article","created":{"date-parts":[[2022,9,14]],"date-time":"2022-09-14T23:16:36Z","timestamp":1663197396000},"page":"3191","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Sorafenib-Loaded Cu2\u2212xSe Nanoparticles Boost Photothermal\u2013Synergistic Targeted Therapy against Hepatocellular Carcinoma"],"prefix":"10.3390","volume":"12","author":[{"given":"An-Tian","family":"Huang","sequence":"first","affiliation":[{"name":"Institute of Bismuth and Rhenium, School of Materials and Chemistry, Shanghai Collaborative Innovation Center of Energy Therapy for Tumors, University of Shanghai for Science and Technology, Shanghai 200093, China"},{"name":"Department of Gastroenterology and Hepatology, Zhongshan Hospital of Fudan University, Shanghai 200032, China"},{"name":"Shanghai Institute of Liver Disease, Shanghai 200032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Du","sequence":"additional","affiliation":[{"name":"Institute of Bismuth and Rhenium, School of Materials and Chemistry, Shanghai Collaborative Innovation Center of Energy Therapy for Tumors, University of Shanghai for Science and Technology, Shanghai 200093, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi-Yong","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Zhongshan Hospital of Fudan University, Shanghai 200032, China"},{"name":"Shanghai Institute of Liver Disease, Shanghai 200032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guang-Cong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Zhongshan Hospital of Fudan University, Shanghai 200032, China"},{"name":"Shanghai Institute of Liver Disease, Shanghai 200032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weinire","family":"Abuduwaili","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Zhongshan Hospital of Fudan University, Shanghai 200032, China"},{"name":"Shanghai Institute of Liver Disease, Shanghai 200032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia-Yan","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Liver Surgery and Transplantation, Zhongshan Hospital of Fudan University, Shanghai 200032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4021-5079","authenticated-orcid":false,"given":"Jia-Lei","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Zhongshan Hospital of Fudan University, Shanghai 200032, China"},{"name":"Shanghai Institute of Liver Disease, Shanghai 200032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ru-Chen","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Zhongshan Hospital of Fudan University, Shanghai 200032, China"},{"name":"Shanghai Institute of Liver Disease, Shanghai 200032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao-Tao","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Zhongshan Hospital of Fudan University, Shanghai 200032, China"},{"name":"Shanghai Institute of Liver Disease, Shanghai 200032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi-Zhong","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Zhongshan Hospital of Fudan University, Shanghai 200032, China"},{"name":"Shanghai Institute of Liver Disease, Shanghai 200032, China"},{"name":"Key Laboratory of Medical Molecular Virology, Shanghai Medical College of Fudan University, Shanghai 200032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5995-7673","authenticated-orcid":false,"given":"Ling","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Zhongshan Hospital of Fudan University, Shanghai 200032, China"},{"name":"Shanghai Institute of Liver Disease, Shanghai 200032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2150-473X","authenticated-orcid":false,"given":"Ji-Min","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Zhongshan Hospital of Fudan University, Shanghai 200032, China"},{"name":"Shanghai Institute of Liver Disease, Shanghai 200032, 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