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2. Targeted delivery of chemically modified anti-miR-221 to hepatocellular carcinoma with negatively charged liposomes

Author

Zhang,Wendian, Peng,Fangqi, Zhou,Taotao, Huang,Yifei, Zhang,Li, Ye,Peng, Lu,Miao, Yang,Guang, Gai,Yongkang, Yang,Tan, Ma,Xiang, Xiang,Guangya, Zhang,Wendian, Peng,Fangqi, Zhou,Taotao, Huang,Yifei, Zhang,Li, Ye,Peng, Lu,Miao, Yang,Guang, Gai,Yongkang, Yang,Tan, Ma,Xiang, and Xiang,Guangya

Abstract

Wendian Zhang,1 Fangqi Peng,1 Taotao Zhou,1 Yifei Huang,2 Li Zhang,3 Peng Ye,4 Miao Lu,1 Guang Yang,5 Yongkang Gai,1 Tan Yang,1 Xiang Ma,1 Guangya Xiang1 1School of Pharmacy, Tongji Medical College, 2Department of Pharmacy, 3Department of Ultrasound, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 4Department of Pharmacy, Wuhan University, Renmin Hospital, 5School of Medicine, Jianghan University, Wuhan, People’s Republic of China 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, P27kip1, 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, P27kip1, 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. Keywords: transferrin, gene, HCC, target delivery system, anionic liposome&nbsp

Published
2015

4. Targeted delivery of chemically modified anti-miR-221 to hepatocellular carcinoma with negatively charged liposomes.

Author

Zhang W, Peng F, Zhou T, Huang Y, Zhang L, Ye P, Lu M, Yang G, Gai Y, Yang T, Ma X, and Xiang G

Subjects
Animals, Hep G2 Cells, Humans, Mice, Receptors, Transferrin genetics, Xenograft Model Antitumor Assays, Carcinoma, Hepatocellular metabolism, Genetic Therapy methods, Liposomes chemistry, Liposomes pharmacokinetics, Liposomes pharmacology, Liver Neoplasms metabolism, MicroRNAs antagonists & inhibitors, Oligonucleotides, Antisense genetics, Oligonucleotides, Antisense pharmacokinetics, Oligonucleotides, Antisense pharmacology
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.

Published
2015
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