title: Novel peptide targeting integrin αvβ3-rich tumor cells by magnetic resonance imaging.
abstract: OBJECTIVE
  To investigate the targeting activity of the peptide (named P1c) derived from connective tissue growth factor (CTGF) to αvβ3-rich tumor cells.
  
  
  METHODS
  P1c was synthesized and conjugated with ultrasuperparamagnetic iron oxide particles (USPIOs) coated with meso-2,3-dimercaptosuccinic acid (DMSA). The specific binding activity of P1c-USPIOs to αvβ3 was verified by solid phase binding assay. The combination of P1c-USPIOs with a human primary liver cancer cell (Bel 7402) with αvβ3-positive expression and uptake of P1c-USPIOs by cells was investigated by Prussian blue staining, transmission electron microscopy (TEM), and magnetic resonance imaging (MRI). The targeting activity of the probe in vivo was also evaluated using a small-animal tumor model by MRI.
  
  
  RESULTS
  The cell uptake of P1c-USPIOs was observed in a dose-dependent manner, whereas no significant particle uptake was found in the plain USPIOs group. The differences on T2*-weighted imaging were also found by MRI and the signal intensity (SI) was statistically reduced after coculture of Bel 7402 cells with P1c-USPIOs at a concentration of 20-80 μg/mL compared with plain USPIOs (P < 0.05). The in vivo study showed that the signal reduction was distributed mainly in the periphery and some central areas of the tumor. The tumor-to-muscle CNR (contrast-to-noise ratio) at 12 hours after the administration of the P1c-USPIOs was statistically significantly different compared to those at 0 hour, 1 hour, or the plain USPIO group (P < 0.05).
  
  
  CONCLUSIONS
  The peptide P1c might be a good candidate as a targeting carrier for drugs or tracers.
authors.affiliation: Center of Clinical Laboratory Medicine of Zhongda Hospital, Institute of Biotechnology and Clinical Pharmacy, Southeast University, Nanjing, China. nationball@163.com
authors.forename: Guoqiu
authors.initials: G
authors.lastname: Wu
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Wang
authors.forename: Gang
authors.initials: G
authors.lastname: Deng
authors.forename: Linyuan
authors.initials: L
authors.lastname: Wu
authors.forename: Shenghong
authors.initials: S
authors.lastname: Ju
authors.forename: Gaojun
authors.initials: G
authors.lastname: Teng
authors.forename: Yuyu
authors.initials: Y
authors.lastname: Yao
authors.forename: Xiyong
authors.initials: X
authors.lastname: Wang
authors.forename: Naifeng
authors.initials: N
authors.lastname: Liu
mesh_terms: D045744:Cell Line, Tumor; D004396:Coloring Agents / Q000494:pharmacology; D018450:Disease Progression; D005290:Ferric Compounds / Q000737:chemistry; D005295:Ferrocyanides / Q000494:pharmacology; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000378:metabolism*; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology; D008279:Magnetic Resonance Imaging / Q000379:methods*; D046529:Microscopy, Electron, Transmission / Q000379:methods; D009362:Neoplasm Metastasis; D010455:Peptides / Q000737:chemistry*; D004113:Succimer / Q000494:pharmacology
chemical_list: D004396:Coloring Agents; D005290:Ferric Compounds; D005295:Ferrocyanides; D039302:Integrin alphaVbeta3; D010455:Peptides; C000499:ferric oxide; D004113:Succimer; C000170:ferric ferrocyanide