title: alphaVbeta3-targeted copper nanoparticles incorporating an Sn 2 lipase-labile fumagillin prodrug for photoacoustic neovascular imaging and treatment.
abstract: Photoacoustic (PA) tomography enables multiscale, multicontrast and high-resolution imaging of biological structures. In particular, contrast-enhanced PA imaging offers high-sensitivity noninvasive imaging of neovessel sprout formation and nascent tubules, which are important biomarkers of malignant tumors and progressive atherosclerotic disease. While gold nanoparticles or nanorods have been used as PA contrast agents, we utilized high-density copper oleate small molecules encapsulated within a phospholipid surfactant (CuNPs) to generate a soft nanoparticle with PA contrast comparable to that from gold. Within the NIR window, the copper nanoparticles provided a 4-fold higher signal than that of blood. ανβ3-integrin targeting of CuNPs in a Matrigel(TM) angiogenesis mouse model demonstrated prominent (p<0.05) PA contrast enhancement of the neovasculature compared with mice given nontargeted or competitively inhibited CuNPs. Furthermore, incorporation of a Sn 2 lipase-labile fumagillin prodrug into the CuNP outer lipid membrane produced marked antiangiogenesis in the same model when targeted to the ανβ3-integrin, providing proof of concept in vivo for the first targeted PA - drug delivery agent.
authors.affiliation: 1. Department of Biomedical Engineering, Washington University, St Louis, MO 63130;
authors.forename: Ruiying
authors.initials: R
authors.lastname: Zhang
authors.affiliation: 2. Department of Medicine, Washington University School of Medicine, St Louis, MO 63108; ; 3. Current address: Department of Bioengineering and Beckman Institute, University of Illinois, Urbana, IL 61801.
authors.forename: Dipanjan
authors.initials: D
authors.lastname: Pan
authors.affiliation: 1. Department of Biomedical Engineering, Washington University, St Louis, MO 63130;
authors.forename: Xin
authors.initials: X
authors.lastname: Cai
authors.affiliation: 2. Department of Medicine, Washington University School of Medicine, St Louis, MO 63108;
authors.forename: Xiaoxia
authors.initials: X
authors.lastname: Yang
authors.affiliation: 2. Department of Medicine, Washington University School of Medicine, St Louis, MO 63108;
authors.forename: Angana
authors.initials: A
authors.lastname: Senpan
authors.affiliation: 2. Department of Medicine, Washington University School of Medicine, St Louis, MO 63108;
authors.forename: John S
authors.initials: JS
authors.lastname: Allen
authors.affiliation: 1. Department of Biomedical Engineering, Washington University, St Louis, MO 63130; ; 2. Department of Medicine, Washington University School of Medicine, St Louis, MO 63108;
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Lanza
authors.affiliation: 1. Department of Biomedical Engineering, Washington University, St Louis, MO 63130;
authors.forename: Lihong V
authors.initials: LV
authors.lastname: Wang
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D003300:Copper / Q000378:metabolism*; D003510:Cyclohexanes / Q000378:metabolism*; D004195:Disease Models, Animal; D005231:Fatty Acids, Unsaturated / Q000378:metabolism*; D039302:Integrin alphaVbeta3 / Q000378:metabolism*; D008049:Lipase / Q000378:metabolism; D008819:Mice, Nude; D053758:Nanoparticles / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000175:diagnosis* / Q000628:therapy*; D061088:Photoacoustic Techniques / Q000379:methods; D011355:Prodrugs / Q000378:metabolism; D012717:Sesquiterpenes / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; D003510:Cyclohexanes; D005231:Fatty Acids, Unsaturated; D039302:Integrin alphaVbeta3; D011355:Prodrugs; D012717:Sesquiterpenes; D003300:Copper; C026211:fumagillin; D008049:Lipase
keywords: angiogenesis imaging; anti-angiogenic therapy.; copper; nanoparticle; near-infrared imaging; photoacoustic imaging