EGFR-specific PEGylated immunoliposomes for active siRNA delivery in hepatocellular carcinoma.

Abstract

The development of immunoliposomes for systemic siRNA (small interfering RNA) delivery is highly desired. We reported previously the development of targeted LPD (liposome-polycation-DNA complex) conjugated with anti-EGFR (epidermal growth factor receptor) Fab' (TLPD-FCC) for siRNA delivery, which showed superior gene silencing activity in EGFR-overexpressing breast cancers. However, TLPD-FCC did not achieve satisfactory gene silencing activity in EGFR-overexpressing hepatocellular carcinoma (HCC). In this study, some modifications including increased antibody conjugation efficiency and reduced PEGylation degree were made to TLPD-FCC to increase gene silencing activity in HCC. The resultant optimized liposomes denoted as TLPD-FP75 efficiently bound and delivered to EGFR-overexpressing HCC, resulting in enhanced gene silencing activity compared to untargeted LPD (NTLPD-FP75). Tissue distribution in vivo revealed that the accumulation of TLPD-FP75 was higher than NTLPD-FP75 in orthotopic HCC model of mice. The promoted uptake of TLPD-FP75 in HCC cells was confirmed by confocal microscopy. To investigate the in vivo gene silencing activity, we administered TLPD-FP75 by intravenous injections into mice bearing orthotopic HCC. The results showed TLPD-FP75 potently suppressed luciferase expression, while little silencing was observed in NTLPD-FP75. TLPD-FP75 was demonstrated to possess potent gene silencing activity in HCC and will potentially increase the feasibility of HCC gene therapy.

• Authors: Jie Gao, Yongsheng Yu, Yingying Zhang, Jinjing Song, Huaiwen Chen, Wei Li, Weizhu Qian, Li Deng, Geng Kou, Jianming Chen, Yajun Guo
• Journal: Biomaterials (Biomaterials) Vol. 33 Issue 1 Pg. 270-82 (Jan 2012) ISSN: 1878-5905 [Electronic] Netherlands
• PMID: 21963149 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Ltd. All rights reserved.

Chemical References

• Liposomes
• RNA, Small Interfering
• Polyethylene Glycols
• ErbB Receptors

Topics

• Animals
• Carcinoma, Hepatocellular (genetics, therapy)
• Cell Line, Tumor
• ErbB Receptors
• Gene Silencing
• Humans
• Liposomes (administration & dosage, chemistry)
• Liver Neoplasms (genetics, therapy)
• Male
• Mice
• Polyethylene Glycols (chemistry)
• RNA, Small Interfering (administration & dosage, genetics, physiology)