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Retargeting of adenoviral gene delivery via Herceptin-PEG-adenovirus conjugates to breast cancer cells

Authors
 Yukyung Jung  ;  Hyo-Jin Park  ;  Seungjoo Haam  ;  Chae-Ok Yun  ;  Yong-Min Huh  ;  Joo-Hang Kim  ;  Joo-Hyuk Sohn  ;  Hyunju Ko  ;  Jaemoon Yang  ;  Woochan Hyung  ;  Jaewon Lee  ;  Pyung-Hwan Kim 
Citation
 JOURNAL OF CONTROLLED RELEASE, Vol.123(2) : 164-171, 2007 
Journal Title
JOURNAL OF CONTROLLED RELEASE
ISSN
 0168-3659 
Issue Date
2007
MeSH
Adenoviridae/genetics* ; Adenoviridae/immunology ; Animals ; Antibodies, Monoclonal/chemistry ; Antibodies, Monoclonal/metabolism ; Antibodies, Monoclonal/pharmacology* ; Antibodies, Monoclonal/therapeutic use ; Antibodies, Monoclonal, Humanized ; Antineoplastic Agents/chemistry ; Antineoplastic Agents/metabolism ; Antineoplastic Agents/pharmacology* ; Antineoplastic Agents/therapeutic use ; Breast Neoplasms/genetics ; Breast Neoplasms/metabolism ; Breast Neoplasms/therapy* ; Cell Line, Tumor ; Chromatography, Liquid ; Feasibility Studies ; Female ; Flow Cytometry ; Gene Expression Regulation, Neoplastic ; Genes, Reporter ; Genetic Therapy/methods* ; Genetic Vectors*/immunology ; Green Fluorescent Proteins/genetics ; Humans ; Interleukin-6/metabolism ; Light ; Macrophages/immunology ; Macrophages/metabolism ; Mice ; Microscopy, Electron, Transmission ; Polyethylene Glycols/chemistry* ; Receptor, ErbB-2/genetics ; Receptor, ErbB-2/metabolism ; Scattering, Radiation ; Transduction, Genetic* ; Trastuzumab
Keywords
Adenovirus ; PEG ; Herceptin ; Targeting ; Gene therapy
Abstract
Targeted adenoviral gene delivery using human epidermal growth factor receptor 2 (HER2/neu) is one of the promising strategies for enhancing the transduction efficacy of PEGylated adenovirus (PEG–ADV). The viral capsid of adenovirus carrying the green fluorescent protein (GFP) was conjugated with bifunctional polyethylene glycol (PEG). The surface of PEG–ADV was then further conjugated with anti-HER2/neu monoclonal antibody (MAb), Herceptin (Trastuzumab; HER) to grant HER2/neu over-expressed breast cancer cells specific targeting. The PEG–ADV and Herceptin immobilized PEG–ADV (HER–PEG–ADV) extents of retargeting were evaluated, as compared to those of naked ADV. In summary, HER–PEG–ADV exhibited more enhanced level of GFP expression than PEG–ADV did for MDA-MB-435 and MDA-MB-468 cells (a HER2/neu positive cell line), but not for a HER2/neu deficient U251N cells. PEGylated ADV significantly reduced innate immune response likewise, as judged from the amount of interleukin 6 released from macrophage cells. Consequently, this study suggests that HER–PEG–ADV conjugates enable ADV to become more potential therapeutic tools through overcoming the limitation of ADV against immune system and non-specificity.
Full Text
http://www.sciencedirect.com/science/article/pii/S0168365907004063
DOI
10.1016/j.jconrel.2007.08.002
Appears in Collections:
1. College of Medicine (의과대학) > Research Institute (부설연구소) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Radiology (영상의학교실) > 1. Journal Papers
Yonsei Authors
Kim, Joo Hang(김주항)
Sohn, Joo Hyuk(손주혁) ORCID logo https://orcid.org/0000-0002-2303-2764
Yang, Jae Moon(양재문) ORCID logo https://orcid.org/0000-0001-7365-0395
Yun, Chae Ok(윤채옥)
Huh, Yong Min(허용민) ORCID logo https://orcid.org/0000-0002-9831-4475
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/96291
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