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

作者：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 G; Jiang Huabei^*; Cai Jun

来源：Cancer Letters, 2013, 332(1): 120-129.

DOI：10.1016/j.canlet.2012.11.016

• Breast cancer
• Angiogenesis
• Unfolded protein response
• siRNA
• scAAV2
• Photoacoustic imaging

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)-IRE1 alpha, 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.

• 出版日期2013-5-10