Development of an anti-angiogenic therapeutic model combining scAAV2-delivered siRNAs and noninvasive photoacoustic imaging of tumor vasculature development

Qing Ruan, Lei Xi, Sanford L. Boye, Song Han, Zhi J. Chen, William W. Hauswirth, Alfed S. Lewin, Michael E. Boulton, Brian K. Law, Wen G. Jiang, Huabei Jiang, Jun Cai

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

Abstract

We aimed to develop an anti-angiogenic model for breast cancer by combining (1) siRNA-based therapy delivered by self-complementary adeno-associated virus serotype 2 (scAAV2) vectors to target tumor vasculature, and (2) noninvasive monitoring to tumor response to anti-angiogenesis by photoacoustic (PA) imaging. scAAV2 vector containing 7 surface exposed tyrosine to phenylanine capsid mutations was able to transduce microvascular endothelial cells with high efficiency. siRNAs against UPR (unfolded protein response)-IRE1α, XBP-1, ATF6 significantly inhibited breast cancer-induced angiogenesis in vitro by inhibiting endothelial cell survival. PA imaging showed that knockdown of UPR proteins greatly reduced tumor angiogenesis in vivo in breast cancer models.

Original languageEnglish (US)
Pages (from-to)120-129
Number of pages10
JournalCancer Letters
Volume332
Issue number1
DOIs
StatePublished - May 10 2013

Keywords

  • Angiogenesis
  • Breast cancer
  • Photoacoustic imaging
  • ScAAV2
  • SiRNA
  • Unfolded protein response

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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