title: Insights into the therapeutic potential of hypoxia-inducible factor-1α small interfering RNA in malignant melanoma delivered via folate-decorated cationic liposomes.
abstract: Malignant melanoma (MM) represents the most dangerous form of skin cancer, and its incidence is expected to rise in the coming time. However, therapy for MM is limited by low topical drug concentration and multidrug resistance. This article aimed to develop folate-decorated cationic liposomes (fc-LPs) for hypoxia-inducible factor-1α (HIF-1α) small interfering (siRNA) delivery, and to evaluate the potential of such siRNA/liposome complexes in MM therapy. HIF-1α siRNA-loaded fc-LPs (siRNA-fc-LPs) were prepared by a film hydration method followed by siRNA incubation. Folate decoration of liposomes was achieved by incorporation of folate/oleic acid-diacylated oligochitosans. The resulting siRNA-fc-LPs were 95.3 nm in size with a ζ potential of 2.41 mV. The liposomal vectors exhibited excellent loading capacity and protective effect toward siRNA. The in vitro cell transfection efficiency was almost parallel to the commercially available Lipofectamine™ 2000. Moreover, the anti-melanoma activity of HIF-1α siRNA was significantly enhanced through fc-LPs. Western blot analysis and apoptosis test demonstrated that siRNA-fc-LPs substantially reduced the production of HIF-1α-associated protein and induced the apoptosis of hypoxia-tolerant melanoma cells. Our designed liposomal vectors might be applicable as siRNA delivery vehicle to systemically or topically treat MM.
authors.affiliation: Department of Pharmaceutics, Shanghai Dermatology Hospital, Jinan University, Gangzhou, People's Republic of China.
authors.forename: Zhongjian
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Division of Pharmaceutics, College of Pharmacy, Jinan University, Gangzhou, People's Republic of China.
authors.forename: Tianpeng
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Division of Pharmaceutics, College of Pharmacy, Jinan University, Gangzhou, People's Republic of China.
authors.forename: Baojian
authors.initials: B
authors.lastname: Wu
authors.affiliation: Division of Pharmaceutics, College of Pharmacy, Jinan University, Gangzhou, People's Republic of China.
authors.forename: Xingwang
authors.initials: X
authors.lastname: Zhang
mesh_terms: D017209:Apoptosis / Q000235:genetics; D045744:Cell Line, Tumor; D004337:Drug Carriers / Q000737:chemistry; D005492:Folic Acid / Q000737:chemistry*; D015316:Genetic Therapy; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000172:deficiency / Q000235:genetics*; D008081:Liposomes / Q000737:chemistry*; D008545:Melanoma / Q000235:genetics / Q000628:therapy*; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000737:chemistry / Q000235:genetics*; D014162:Transfection
chemical_list: D004337:Drug Carriers; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D008081:Liposomes; D034741:RNA, Small Interfering; D005492:Folic Acid
keywords: HIF-1α siRNA; cationic liposomes; chitosan; gene therapy; malignant melanoma