Journal
THERANOSTICS
Volume 5, Issue 2, Pages 124-133Publisher
IVYSPRING INT PUBL
DOI: 10.7150/thno.10014
Keywords
copper; nanoparticle; near-infrared imaging; photoacoustic imaging; angiogenesis imaging; anti-angiogenic therapy
Categories
Funding
- NIH
- DOD [DP1 EB016986, R01 CA186567, R01 EB016963, R01 CA159959, HL112518, HL113392, CA154737, CA136398, NS073457, CA100623]
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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. alpha(v)beta(3)-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 alpha(v)beta(3)-integrin, providing proof of concept in vivo for the first targeted PA - drug delivery agent.
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