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Published January 1, 2015 | Published
Journal Article Open

α_νβ_3-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. Α_νβ_3-integrin targeting of CuNPs in a Matrigel™ 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 α_νβ_3-integrin, providing proof of concept in vivo for the first targeted PA - drug delivery agent.

Additional Information

© 2015 Ivyspring International Publisher. This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) License. Received: 2014.06.30; Accepted: 2014.09.18; Published: 2015.01.01. The authors would like to thank Prof. James Ballard for his close reading of the manuscript. L. V. Wang has a financial interest in Microphotacoustic, Inc. and Endra, Inc., which did not support this work. Washington University owns the intellectual property to CuNP and it was licensed nonexclusively to Ocean NanoTech, LLC for research commerce. Kereos, Inc. provided the peptidomimetic homing ligand as a gift, and GML is a scientific co-founder of Kereos. The financial support from the NIH and DOD under grant numbers DP1 EB016986 (NIH Director's Pioneer Award), R01 CA186567 (NIH Director's Transformative Research Award), R01 EB016963, R01 CA159959, HL112518, HL113392, CA154737, CA136398, NS073457, and from the DOD CA100623 was greatly appreciated. The authors have declared that no competing interest exists.

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