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Dual-targeting liposomal delivery of sorafenib and docetaxel for enhanced synergistic therapy in advanced hepatocellular carcinoma
Yao, Yawen1,2; Hu, Yue1; Meng, Xinwang1; Feng, Fenyan1; Xu, Feng1; Wang, Guangji3; Yu, Hua2; Li, Juan1
2024-12-01
Source PublicationPharmaceutical Science Advances
ISSN2773-2169
Volume2Pages:100046
Abstract

Patients with advanced hepatocellular carcinoma (HCC) are not sensitive to sorafenib (SOR), therefore, combination therapy is required. In this study, an improved thin-film dispersion and post-insertion anchoring technique was utilized to construct a dual-targeted co-delivery SOR and docetaxel (DTX) liposome drug delivery system, folate/chondroitin sulfate with SOR/DTX-modified liposomes (FA/CS@SDLP), to jointly enhance the anti-recurrence and metastasis of HCC. FA/CS@SDLP can establish the gradual release of the two drugs because of successful lysosomal escape in the condensed hyaluronidase environment. The results indicated that modification with folate (FA) and chondroitin sulfate (CS) significantly enhanced the cellular uptake of FA/CS@SDLP and the internalization of SOR/DTX in HepG2 cells through FA and CD44 receptor-mediated endocytosis. Compared to free drugs or the mono-targeted liposomal system (FA@SDLP), FA/CS@SDLP presented higher potency against HepG2 cells regarding pro-apoptosis, anti-proliferation, and anti-metastasis (migration and invasion). Moreover, a more satisfactory antitumor efficacy was observed for FA/CS@SDLP in the pulmonary metastasis of HCC in a mouse model. In summary, dual-targeted co-delivery of liposomes can synergistically treat HCC recurrence and metastasis, providing a new approach for the clinically accurate treatment of HCC.

KeywordSorafenib Docetaxel Dual-targeting Liposomes Combination Therapy Advanced Hepatocellular Carcinoma
DOI10.1016/j.pscia.2024.100046
URLView the original
Language英語English
PublisherElsevier B.V.
Scopus ID2-s2.0-85208358561
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Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Corresponding AuthorYu, Hua; Li, Juan
Affiliation1.Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing, 210009, China
2.Institute of Chinese Medical Sciences, State Key Laboratory of Quality Research in Chinese Medicine, University of Macau, Macao SAR, China
3.Center of Pharmacokinetics, Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing, 210009, China
First Author AffilicationInstitute of Chinese Medical Sciences
Corresponding Author AffilicationInstitute of Chinese Medical Sciences
Recommended Citation
GB/T 7714
Yao, Yawen,Hu, Yue,Meng, Xinwang,et al. Dual-targeting liposomal delivery of sorafenib and docetaxel for enhanced synergistic therapy in advanced hepatocellular carcinoma[J]. Pharmaceutical Science Advances, 2024, 2, 100046.
APA Yao, Yawen., Hu, Yue., Meng, Xinwang., Feng, Fenyan., Xu, Feng., Wang, Guangji., Yu, Hua., & Li, Juan (2024). Dual-targeting liposomal delivery of sorafenib and docetaxel for enhanced synergistic therapy in advanced hepatocellular carcinoma. Pharmaceutical Science Advances, 2, 100046.
MLA Yao, Yawen,et al."Dual-targeting liposomal delivery of sorafenib and docetaxel for enhanced synergistic therapy in advanced hepatocellular carcinoma".Pharmaceutical Science Advances 2(2024):100046.
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