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

Ruan, Qing, Xi, Lei, Boye, Sanford L., Han, Song, Chen, Zhi J., Hauswirth, William W., Lewin, Alfed S., Boulton, Michael E., Law, Brian K., Jiang, Wen Guo, Jiang, Huabei and Cai, Jun 2013. Development of an anti-angiogenic therapeutic model combining scAAV2-delivered siRNAs and noninvasive photoacoustic imaging of tumor vasculature development. Cancer Letters 332 (1) , pp. 120-129. 10.1016/j.canlet.2012.11.016

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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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Subjects: R Medicine > R Medicine (General)
Uncontrolled Keywords: Breast cancer, Angiogenesis, Unfolded protein response, siRNA, scAAV2, Photoacoustic imaging
Publisher: Elsevier
ISSN: 0304-3835
Last Modified: 04 Jun 2017 08:13
URI: http://orca-mwe.cf.ac.uk/id/eprint/74562

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