title: Anti-tumor Efficiency of Lipid-coated Cisplatin Nanoparticles Co-loaded with MicroRNA-375.
abstract: One of the major challenges in the hepatocellular carcinoma (HCC) treatment is its insensitivity to chemotherapeutic drugs. Here, we report the development of novel lipid-coated cisplatin nanoparticles co-loaded with microRNA-375 (NPC/miR-375) as a potential treatment for chemotherapy insensitive HCC. The NPC/miR-375 was fabricated by mixing two reverse microemulsions containing KCl solution and a highly soluble cis-diaminedihydroplatinum (II) coated with a cationic lipid layer. Subsequently, the miR-375 was incorporated into the lipid-coated cisplatin nanoparticles. The NPC/miR375 nanoparticles were expected to further decrease cell proliferation and to enhance the anti-tumor effect of cisplatin in chemotherapy resistant HCC cells. In vitro analysis of intracellular trafficking revealed that NPC/miR-375 were able to escape from the late endosomes instead of lysosomes thus avoiding degradation of the miR-375 in lysosomes. Importantly, NPC/miR-375 enhanced apoptosis and induced cell cycle arrest in HCC cells in vitro. In the double oncogenes Akt/Ras-induced primary HCC mouse model, multiple doses of NPC/miR-375 significantly inhibited tumor growth and delayed the tumor relapse. Our results indicate that cisplatin nanoparticles co-loaded with miR-375 represent a potential therapeutic agent for chemotherapy-insensitive HCC.
authors.affiliation: 1. School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, P. R. China.
authors.forename: Tan
authors.initials: T
authors.lastname: Yang
authors.affiliation: 1. School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, P. R. China.
authors.forename: Pengxuan
authors.initials: P
authors.lastname: Zhao
authors.affiliation: 1. School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, P. R. China.
authors.forename: Zhao
authors.initials: Z
authors.lastname: Rong
authors.affiliation: 1. School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, P. R. China.
authors.forename: Bin
authors.initials: B
authors.lastname: Li
authors.affiliation: 1. School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, P. R. China.
authors.forename: Huiying
authors.initials: H
authors.lastname: Xue
authors.affiliation: 1. School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, P. R. China.
authors.forename: Jia
authors.initials: J
authors.lastname: You
authors.affiliation: 1. School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, P. R. China.
authors.forename: Chuanchuan
authors.initials: C
authors.lastname: He
authors.affiliation: 2. Tongji Hospital, Huazhong University of Science and Technology, Wuhan 430030, P. R. China.
authors.forename: Weijie
authors.initials: W
authors.lastname: Li
authors.affiliation: 2. Tongji Hospital, Huazhong University of Science and Technology, Wuhan 430030, P. R. China.
authors.forename: Xingxing
authors.initials: X
authors.lastname: He
authors.affiliation: 3. Division of Pharmaceutics, College of Pharmacy, the Ohio State University, Columbus, Ohio, USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Lee
authors.affiliation: 1. School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, P. R. China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Ma
authors.affiliation: 1. School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, P. R. China.
authors.forename: Guangya
authors.initials: G
authors.lastname: Xiang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000138:chemical synthesis / Q000494:pharmacology; D017209:Apoptosis; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy*; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000008:administration & dosage* / Q000494:pharmacology; D004195:Disease Models, Animal; D022781:Hepatocytes / Q000187:drug effects; D008081:Liposomes / Q000008:administration & dosage* / Q000138:chemical synthesis / Q000494:pharmacology; D051379:Mice; D035683:MicroRNAs / Q000008:administration & dosage* / Q000494:pharmacology; D053758:Nanoparticles / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D008081:Liposomes; C540933:MIRN375 microRNA, human; D035683:MicroRNAs; D002945:Cisplatin
keywords: Cisplatin; Co-delivery; Hepatocellular Carcinoma; Nanoparticles; miR-375