title: Actively-targeted LTVSPWY peptide-modified magnetic nanoparticles for tumor imaging.
abstract: BACKGROUND
  Magnetic resonance imaging (MRI) is widely used in modern clinical medicine as a diagnostic tool, and provides noninvasive and three-dimensional visualization of biological phenomena in living organisms with high spatial and temporal resolution. Therefore, considerable attention has been paid to magnetic nanoparticles as MRI contrast agents with efficient targeting ability and cellular internalization ability, which make it possible to offer higher contrast and information-rich images for detection of disease.
  
  
  METHODS
  LTVSPWY peptide-modified PEGylated chitosan (LTVSPWY-PEG-CS) was synthesized by chemical reaction, and the chemical structure was confirmed by (1)H-NMR. LTVSPWY-PEG-CS-modified magnetic nanoparticles were prepared successfully using the solvent diffusion method. Their particle size, size distribution, and zeta potential were measured by dynamic light scattering and electrophoretic mobility, and their surface morphology was investigated by transmission electron microscopy. To investigate their selective targeting ability, the cellular uptake of the LTVSPWY-PEG-CS-modified magnetic nanoparticles was observed in a cocultured system of SKOV-3 cells which overexpress HER2 and A549 cells which are HER2-negative. The in vitro cytotoxicity of these nanoparticles in SKOV-3 and A549 cells was measured using the MTT method. The SKOV-3-bearing nude mouse model was used to investigate the tumor targeting ability of the magnetic nanoparticles in vivo.
  
  
  RESULTS
  The average diameter and zeta potential of the LTVSPWY-PEG-CS-modified magnetic nanoparticles was 267.3 ± 23.4 nm and 30.5 ± 7.0 mV, respectively, with a narrow size distribution and spherical morphology. In vitro cytotoxicity tests demonstrated that these magnetic nanoparticles were carriers suitable for use in cancer diagnostics with low toxicity. With modification of the LTVSPWY homing peptide, magnetic nanoparticles could be selectively taken up by SKOV-3 cells overexpressing HER2 when cocultured with HER2-negative A549 cells. In vivo biodistribution results suggest that treatment with LTVSPWY-PEG-CS-modified magnetic nanoparticles/DiR enabled tumors to be identified and diagnosed more rapidly and efficiently in vivo.
  
  
  CONCLUSIONS
  LTVSPWY-PEG-CS-modified magnetic nanoparticles are a promising contrast agent for early detection of tumors overexpressing HER2 and further diagnostic application.
authors.affiliation: Department of Radiology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People's Republic of China.
authors.forename: Li-Yong
authors.initials: LY
authors.lastname: Jie
authors.forename: Li-Li
authors.initials: LL
authors.lastname: Cai
authors.forename: Le-Jian
authors.initials: LJ
authors.lastname: Wang
authors.forename: Xiao-Ying
authors.initials: XY
authors.lastname: Ying
authors.forename: Ri-Sheng
authors.initials: RS
authors.lastname: Yu
authors.forename: Min-Ming
authors.initials: MM
authors.lastname: Zhang
authors.forename: Yong-Zhong
authors.initials: YZ
authors.lastname: Du
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D048271:Chitosan / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D018920:Coculture Techniques; D004337:Drug Carriers / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology; D058185:Magnetite Nanoparticles / Q000737:chemistry*; D051379:Mice; D008819:Mice, Nude; D057054:Molecular Imaging / Q000379:methods*; D019906:Nuclear Magnetic Resonance, Biomolecular; D009842:Oligopeptides / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D010051:Ovarian Neoplasms / Q000378:metabolism / Q000473:pathology; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis; D012235:Rhodamines / Q000737:chemistry / Q000493:pharmacokinetics; D014018:Tissue Distribution
chemical_list: D048271:Chitosan; D004337:Drug Carriers; D058185:Magnetite Nanoparticles; D009842:Oligopeptides; D011092:Polyethylene Glycols; D018719:Erb-b2 Receptor Tyrosine Kinases; D012235:Rhodamines; C027755:rhodamine isothiocyanate