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

Yukyung Jung, Hyo Jin Park, Pyung Hwan Kim, Jaewon Lee, Woochan Hyung, Jaemoon Yang, Hyunju Ko, Joo Hyuk Sohn, Joo Hang Kim, Yong Min Huh, Chae Ok Yun, Seungjoo Haam

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46 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)164-171
Number of pages8
JournalJournal of Controlled Release
Volume123
Issue number2
DOIs
Publication statusPublished - 2007 Nov 6

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All Science Journal Classification (ASJC) codes

  • Pharmaceutical Science

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