ανβ3-targeted Copper Nanoparticles Incorporating an Sn 2 Lipase-Labile Fumagillin Prodrug for Photoacoustic Neovascular Imaging and Treatment

Details

• Alternative Title:
  Theranostics
• Personal Author:
  Zhang, Ruiying ; Pan, Dipanjan ; Cai, Xin ; Yang, Xiaoxia ; Senpan, Angana ; Allen, John S. ; Lanza, Gregory M. ; Wang, Lihong V.
• Description:
  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.
• Subjects:
  Angiogenesis Imaging Angiogenesis Inhibitors Animals Anti-angiogenic Therapy. Copper Cyclohexanes Disease Models, Animal Fatty Acids, Unsaturated Integrin AlphaVbeta3 Lipase Mice, Nude Nanoparticle Nanoparticles Near-infrared Imaging Neovascularization, Pathologic Photoacoustic Imaging Photoacoustic Techniques Prodrugs Research Paper Sesquiterpenes

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• Source:
  Theranostics. 2015; 5(2):124-133.
• Pubmed ID:
  25553103
• Pubmed Central ID:
  PMC4278999
• Document Type:
  Journal Article
• Funding:
  CA136398/CA/NCI NIH HHS/United States ; CA154737/CA/NCI NIH HHS/United States ; DP1 EB016986/DP/NCCDPHP CDC HHS/United States ; DP1 EB016986/EB/NIBIB NIH HHS/United States ; HL112518/HL/NHLBI NIH HHS/United States ; HL113392/HL/NHLBI NIH HHS/United States ; NS073457/NS/NINDS NIH HHS/United States ; R01 CA154737/CA/NCI NIH HHS/United States ; R01 CA159959/CA/NCI NIH HHS/United States ; R01 CA159959/CA/NCI NIH HHS/United States ; R01 CA186567/CA/NCI NIH HHS/United States ; R01 CA186567/CA/NCI NIH HHS/United States ; R01 EB016963/EB/NIBIB NIH HHS/United States ; R01 EB016963/EB/NIBIB NIH HHS/United States ; R01 HL113392/HL/NHLBI NIH HHS/United States ; R42 HL112518/HL/NHLBI NIH HHS/United States ; U01 NS073457/NS/NINDS NIH HHS/United States ; U54 CA136398/CA/NCI NIH HHS/United States
• Volume:
  5
• Issue:
  2
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:d0677a4668f5d67684da06e89c1f764a211576d12b3a5f89996ac617d32db90a
• Download URL:
  https://stacks.cdc.gov/view/cdc/32383/cdc_32383_DS1.pdf
• File Type:
  [PDF - 907.15 KB ]