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Targeted gene silencing using RGD-labeled chitosan nanoparticles

Authors
 Hee Dong Han  ;  Lingegowda S. Mangala  ;  Jeong Won Lee  ;  Mian M.K. Shahzad  ;  Hye Sun Kim  ;  Deyu Shen  ;  Eun Ji Nam  ;  Edna M. Mora  ;  Rebecca L. Stone  ;  Chunhua Lu  ;  Sun Joo Lee  ;  Ju Won Roh  ;  Alpa M. Nick  ;  Gabriel Lopez-Berestein  ;  Anil K. Sood 
Citation
 CLINICAL CANCER RESEARCH, Vol.16(15) : 3910-3922, 2010 
Journal Title
CLINICAL CANCER RESEARCH
ISSN
 1078-0432 
Issue Date
2010
MeSH
Animals ; Antineoplastic Agents/administration & dosage ; Blotting, Western ; Chitosan/administration & dosage* ; Chitosan/chemistry ; Drug Delivery Systems/methods ; Female ; Gene Silencing ; Genetic Therapy/methods* ; Humans ; Mice ; Mice, Nude ; Nanoparticles/administration & dosage* ; Nanoparticles/chemistry ; Neoplasm Proteins/genetics ; Oligopeptides/administration & dosage* ; Oligopeptides/chemistry ; Ovarian Neoplasms/genetics ; Ovarian Neoplasms/therapy* ; RNA, Small Interfering/administration & dosage* ; Receptors, Cell Surface/genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Xenograft Model Antitumor Assays
Abstract
PURPOSE: This study aimed to develop an Arg-Gly-Asp (RGD) peptide-labeled chitosan nanoparticle (RGD-CH-NP) as a novel tumor targeted delivery system for short interfering RNA (siRNA).

EXPERIMENTAL DESIGN: RGD peptide conjugated with chitosan by thiolation reaction was confirmed by proton-NMR (H-NMR). Binding of RGD-CH-NP with alphanubeta3 integrin was examined by flow cytometry and fluorescence microscopy. Antitumor efficacy was examined in orthotopic mouse models of ovarian carcinoma.

RESULTS: We show that RGD-CH-NP loaded with siRNA significantly increased selective intratumoral delivery in orthotopic animal models of ovarian cancer. In addition, we show targeted silencing of multiple growth-promoting genes (POSTN, FAK, and PLXDC1) along with therapeutic efficacy in the SKOV3ip1, HeyA8, and A2780 models using siRNA incorporated into RGD-CH-NP (siRNA/RGD-CH-NP). Furthermore, we show in vivo tumor vascular targeting using RGD-CH-NP by delivering PLXDC1-targeted siRNA into the alphanubeta3 integrin-positive tumor endothelial cells in the A2780 tumor-bearing mice. This approach resulted in significant inhibition of tumor growth compared with controls.

CONCLUSIONS: This study shows that RGD-CH-NP is a novel and highly selective delivery system for siRNA with the potential for broad applications in human disease.
Files in This Item:
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DOI
10.1158/1078-0432.CCR-10-0005
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Obstetrics and Gynecology (산부인과학교실) > 1. Journal Papers
Yonsei Authors
Nam, Eun Ji(남은지) ORCID logo https://orcid.org/0000-0003-0189-3560
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/101908
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