title: Development of an anti-angiogenic therapeutic model combining scAAV2-delivered siRNAs and noninvasive photoacoustic imaging of tumor vasculature development.
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.
authors.affiliation: Department of Anatomy & Cell Biology, University of Florida, Gainesville, FL 32610, USA.
authors.forename: Qing
authors.initials: Q
authors.lastname: Ruan
authors.forename: Lei
authors.initials: L
authors.lastname: Xi
authors.forename: Sanford L
authors.initials: SL
authors.lastname: Boye
authors.forename: Song
authors.initials: S
authors.lastname: Han
authors.forename: Zhi J
authors.initials: ZJ
authors.lastname: Chen
authors.forename: William W
authors.initials: WW
authors.lastname: Hauswirth
authors.forename: Alfed S
authors.initials: AS
authors.lastname: Lewin
authors.forename: Michael E
authors.initials: ME
authors.lastname: Boulton
authors.forename: Brian K
authors.initials: BK
authors.lastname: Law
authors.forename: Wen G
authors.initials: WG
authors.lastname: Jiang
authors.forename: Huabei
authors.initials: H
authors.lastname: Jiang
authors.forename: Jun
authors.initials: J
authors.lastname: Cai
mesh_terms: D051702:Activating Transcription Factor 6 / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001943:Breast Neoplasms / Q000098:blood supply / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D036022:Capsid Proteins / Q000235:genetics; D045744:Cell Line, Tumor; D002470:Cell Survival; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D000229:Dependovirus / Q000235:genetics*; D004722:Endoribonucleases / Q000235:genetics / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D051379:Mice; D008819:Mice, Nude; D008853:Microscopy; D009154:Mutation; D009389:Neovascularization, Pathologic; D018919:Neovascularization, Physiologic / Q000235:genetics; D061088:Photoacoustic Techniques; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism*; D000071701:Regulatory Factor X Transcription Factors; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014161:Transduction, Genetic; D014162:Transfection; D047368:Tumor Burden; D056811:Unfolded Protein Response / Q000235:genetics; D000071717:X-Box Binding Protein 1
chemical_list: D051702:Activating Transcription Factor 6; C497112:Atf6 protein, mouse; D036022:Capsid Proteins; D004268:DNA-Binding Proteins; D034741:RNA, Small Interfering; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors; D000071717:X-Box Binding Protein 1; C000605544:Xbp1 protein, mouse; C510185:Ern1 protein, mouse; D017346:Protein Serine-Threonine Kinases; D004722:Endoribonucleases