αvβ3-targeted Copper Nanoparticles Incorporating an Sn 2 Lipase-Labile Fumagillin Prodrug for Photoacoustic Neovascular Imaging and Treatment

Ruiying Zhang, Dipanjan Pan, Xin Cai, Xiaoxia Yang, Angana Senpan, John S. Allen, Gregory M. Lanza, Lihong V. Wang

Research output: Contribution to journalArticle

33 Scopus citations

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. αvβ3-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 αvβ3-integrin, providing proof of concept in vivo for the first targeted PA - drug delivery agent.

Original languageEnglish
Pages (from-to)124-133
Number of pages10
JournalTheranostics
Volume5
Issue number2
DOIs
StatePublished - Jan 1 2015

Keywords

  • Angiogenesis imaging
  • Anti-angiogenic therapy
  • Copper
  • Nanoparticle
  • Near-infrared imaging
  • Photoacoustic imaging

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