Systemic delivery of a breast cancer-detecting adenovirus using targeted microbubbles

J. M. Warram, A. G. Sorace, R. Saini, A. V. Borovjagin, K. Hoyt, K. R. Zinn

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

One of the major limitations of cancer gene therapy using recombinant human adenovirus (Ad) is rapid Ad inactivation from systemic delivery. To eliminate this, biotin-coated ultrasound contrast agents, or microbubbles (MBs), were streptavidin-coupled with biotinylated antibodies to three distinct tumor vasculature-associated receptors (α V Β 3 integrin, P-selectin and vascular endothelial growth factor receptor-2) for systemic targeting of a previously generated vector Ad5/3-Id1-SEAP-Id1-mCherry. This cancer-specific, dual-reporter vector was loaded in the targeted MBs and confirmed by confocal microscopy. MB loading capacity was estimated by functional assays as 4.720.2 plaque forming unit (PFU) per MB. Non-loaded (free) Ad particles were effectively inactivated by treatment with human complement. The Ad-loaded, targeted-MBs were injected systemically in mice bearing MDA-MB-231 tumors (Grp 1) and compared with two control groups: Ad-loaded, non-targeted MBs (Grp 2) and free Ad (Grp 3) administered under the same conditions. Two days after administration the blood levels of secreted embryonic alkaline phosphatase (SEAP) reporter in Grp 1 mice (16.1 ng ml-1 2.5) were significantly higher (P<0.05) than those in Grp 2 (9.75 ng ml-1 1.5) or Grp 3 (4.26 ng ml-1 2.5) animals. The targeted Ad delivery was also confirmed by fluorescence imaging. Thus, Ad delivery by targeted MBs holds potential as a safe and effective system for systemic Ad delivery for the purpose of cancer screening.

Original languageEnglish (US)
Pages (from-to)545-552
Number of pages8
JournalCancer Gene Therapy
Volume19
Issue number8
DOIs
StatePublished - Aug 2012

Keywords

  • adenovirus
  • detection
  • fluorescence
  • microbubble

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Cancer Research

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