title: P53-Derived peptides conjugation to PEI: an approach to producing versatile and highly efficient targeted gene delivery carriers into cancer cells.
abstract: OBJECTIVE
  Targeted delivery of cytotoxic drugs or therapeutic antisense RNAs into specific cells is a major bottleneck in cancer therapy. To overcome this problem and improve the specificity for cancer cells, we describe a new-targeted delivery system using p53-derived peptides, namely PNC 27 and PNC 28. These peptides target HDM-2 on the surface of cancer cells. HDM-2 is overexpressed on the surface of cancerous cells, but not present on the untransformed cells.
  
  
  METHODS
  To determine HDM-2-expressing cells, we used immunocytochemistry and flow cytometry analysis on nine cell lines including MCF-7 and NIH-3t3. Conjugation of peptides to vectors was confirmed using reverse-phase high-pressure liquid chromatography (RP-HPLC). Physicochemical properties of vector/DNA complexes including particle size, surface charge and DNA condensation ability were determined. In transfection studies, three plasmids were used including luciferase, pEGFP and shRNA plasmid against Bcl-XL mRNA. The level of Bcl-XL expression was determined by real-time PCR and western blot techniques.
  
  
  RESULTS
  The results of gene delivery and shRNA-based gene silencing studies indicated that conjugation of PNC peptides could enhance gene delivery efficiently with high-targeted activity exclusively into cancer cells.
  
  
  CONCLUSIONS
  Our results strongly indicated that this targeting system could be utilized as an efficient targeting method for most cancer cells.
authors.affiliation: a School of Medicine , Gonabad University of Medical Sciences , Gonabad , Iran.|b Pharmaceutical Research Center, Department of Pharmaceutical Biotechnology, School of Pharmacy , Mashhad University of Medical Sciences , Mashhad , Iran.|c Department of Biotechnology , Higher Education Institute of Rab-Rashid , Tabriz , Iran.
authors.forename: Ahad
authors.initials: A
authors.lastname: Mokhtarzadeh
authors.affiliation: b Pharmaceutical Research Center, Department of Pharmaceutical Biotechnology, School of Pharmacy , Mashhad University of Medical Sciences , Mashhad , Iran.
authors.forename: Hamideh
authors.initials: H
authors.lastname: Parhiz
authors.affiliation: d Nanotechnology Research Center, School of Pharmacy , Mashhad University of Medical Sciences , Mashhad , Iran.
authors.forename: Maryam
authors.initials: M
authors.lastname: Hashemi
authors.affiliation: b Pharmaceutical Research Center, Department of Pharmaceutical Biotechnology, School of Pharmacy , Mashhad University of Medical Sciences , Mashhad , Iran.
authors.forename: Khalil
authors.initials: K
authors.lastname: Abnous
authors.affiliation: b Pharmaceutical Research Center, Department of Pharmaceutical Biotechnology, School of Pharmacy , Mashhad University of Medical Sciences , Mashhad , Iran.|d Nanotechnology Research Center, School of Pharmacy , Mashhad University of Medical Sciences , Mashhad , Iran.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Ramezani
mesh_terms: D045744:Cell Line, Tumor; D056148:Chromatography, Reverse-Phase; D020099:Coated Materials, Biocompatible; D020868:Gene Silencing; D018014:Gene Transfer Techniques; D006801:Humans; D010316:Particle Size; D010957:Plasmids; D051736:Proto-Oncogene Proteins c-mdm2 / Q000096:biosynthesis*; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D051020:bcl-X Protein / Q000096:biosynthesis
chemical_list: D020099:Coated Materials, Biocompatible; C549751:PNC-27; C513570:PNC-28; D016159:Tumor Suppressor Protein p53; D051020:bcl-X Protein; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2
keywords: Cancer; PNC peptide; shRNA; targeted gene delivery