title: EphA2 targeting pegylated nanocarrier drug delivery system for treatment of lung cancer.
abstract: OBJECTIVE
  Evaluation of tumor targeting pegylated EphA2 peptide coated nanoparticles (ENDDs) of a novel anticancer agent DIM-C-pPhC6H5 (DIM-P) and Docetaxel (DOC) and investigate its antitumor activity and potential for treatment of lung cancer.
  
  
  METHODS
  Nanoparticles were prepared with DIM-P and DOC (NDDs) using Nano-DeBEE. ENDDs were prepared by conjugating NDDs with 6His-PEG2K-EphA2 peptide and characterized for physicochemical properties, binding assay, cytotoxicity, cellular uptake studies, drug release and pharmacokinetic parameters. Anti-tumor activity of ENDDs was evaluated using a metastatic H1650 and orthotopic A549 tumor models in nude mice and tumor tissue were analyzed by RT-PCR and immunohistochemistry.
  
  
  RESULTS
  Particle size and entrapment efficiency of ENDDs were 197 ± 21 nm and 95 ± 2%. ENDDs showed 32.5 ± 3.5% more cellular uptake than NDDs in tumor cells. ENDDs showed 23 ± 3% and 26 ± 4% more tumor reduction compared to NDDs in metastatic and orthotopic tumor models, respectively. In-vivo imaging studies using the Care stream MX FX Pro system showed (p < 0.001) 40-60 fold higher flux for ENDDs compared to NDDs at tumor site.
  
  
  CONCLUSIONS
  The results emanating from these studies demonstrate anti-cancer potential of DIM-P and the role of ENDDs as effective tumor targeting drug delivery systems for lung cancer treatment.
authors.affiliation: College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Tallahassee, Florida, 32307, USA.
authors.forename: Apurva R
authors.initials: AR
authors.lastname: Patel
authors.forename: Mahavir
authors.initials: M
authors.lastname: Chougule
authors.forename: Mandip
authors.initials: M
authors.lastname: Singh
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers / Q000737:chemistry*; D004705:Endocytosis; D006801:Humans; D007211:Indoles / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D008024:Ligands; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D058990:Molecular Targeted Therapy; D053758:Nanoparticles / Q000737:chemistry*; D047495:PPAR gamma / Q000819:agonists; D011092:Polyethylene Glycols / Q000737:chemistry*; D011485:Protein Binding; D036104:Receptor, EphA2 / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays
chemical_list: C505817:1,1-bis(3'-indolyl)-1-(4-biphenyl)methane; D000970:Antineoplastic Agents; D004337:Drug Carriers; D007211:Indoles; D008024:Ligands; D047495:PPAR gamma; D011092:Polyethylene Glycols; D036104:Receptor, EphA2