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已发表论文
靶向递送化学修饰的 anti-miR-221 至具有带负电荷的脂质体的肝细胞癌
Authors Zhang W, Peng F, Zhou T, Huang Y, Zhang L, Ye P, Lu M, Yang G, Gai Y, Yang T, Ma X, Xiang G
Published Date July 2015 Volume 2015:10 Pages 4825—4836
DOI http://dx.doi.org/10.2147/IJN.S79598
Received 19 December 2014, Accepted 30 April 2015, Published 29 July 2015
Approved for publication by Dr Lei Yang
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
