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

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.