title: Targeted delivery of chemically modified anti-miR-221 to hepatocellular carcinoma with negatively charged liposomes.
abstract: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death. Gene therapy was established as a new strategy for treating HCC. To explore the potential delivery system to support the gene therapy of HCC, negatively charged liposomal delivery system was used to deliver miR-221 antisense oligonucleotide (anti-miR-221) to the transferrin (Tf) receptor over expressed HepG2 cells. The liposome exhibited a mean particle size of 122.5 nm, zeta potential of -15.74 mV, anti-miR-221 encapsulation efficiency of 70%, and excellent colloidal stability at 4°C. Anti-miR-221-encapsulated Tf-targeted liposome demonstrated a 15-fold higher delivery efficiency compared to nontargeted liposome in HepG2 cells in vitro. Anti-miR-221 Tf-targeted liposome effectively delivered anti-miR-221 to HepG2 cells, upregulated miR-221 target genes PTEN, P27(kip1), and TIMP3, and exhibited greater silencing efficiency over nontargeted anti-miR-221 liposome. After intravenous injection into HepG2 tumor-bearing xenografted mice with Cy3-labeled anti-miR-221 Tf-targeted liposome, Cy3-anti-miR-221 was successfully delivered to the tumor site and increased the expressions of PTEN, P27(kip1), and TIMP3. Our results demonstrate that the Tf-targeted negatively charged liposome could be a potential therapeutic modality in the gene therapy of human HCC.
authors.affiliation: school of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
authors.forename: Wendian
authors.initials: W
authors.lastname: Zhang
authors.affiliation: school of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
authors.forename: Fangqi
authors.initials: F
authors.lastname: Peng
authors.affiliation: school of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
authors.forename: Taotao
authors.initials: T
authors.lastname: Zhou
authors.affiliation: Department of Pharmacy, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
authors.forename: Yifei
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Ultrasound, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Pharmacy, Wuhan University, Renmin Hospital, Wuhan, People's Republic of China.
authors.forename: Peng
authors.initials: P
authors.lastname: Ye
authors.affiliation: school of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
authors.forename: Miao
authors.initials: M
authors.lastname: Lu
authors.affiliation: School of Medicine, Jianghan University, Wuhan, People's Republic of China.
authors.forename: Guang
authors.initials: G
authors.lastname: Yang
authors.affiliation: school of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
authors.forename: Yongkang
authors.initials: Y
authors.lastname: Gai
authors.affiliation: school of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
authors.forename: Tan
authors.initials: T
authors.lastname: Yang
authors.affiliation: school of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Ma
authors.affiliation: school of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
authors.forename: Guangya
authors.initials: G
authors.lastname: Xiang
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D015316:Genetic Therapy / Q000379:methods*; D056945:Hep G2 Cells; D006801:Humans; D008081:Liposomes / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D008113:Liver Neoplasms / Q000378:metabolism*; D051379:Mice; D035683:MicroRNAs / Q000037:antagonists & inhibitors*; D016376:Oligonucleotides, Antisense / Q000235:genetics / Q000493:pharmacokinetics / Q000494:pharmacology; D011990:Receptors, Transferrin / Q000235:genetics; D023041:Xenograft Model Antitumor Assays
chemical_list: D008081:Liposomes; D035683:MicroRNAs; D016376:Oligonucleotides, Antisense; D011990:Receptors, Transferrin; C525709:MIR221, human
keywords: HCC; anionic liposome; gene; target delivery system; transferrin