title: Novel luminescent silica nanoparticles (LSN): p53 gene delivery system in breast cancer in vitro and in vivo.
abstract: OBJECTIVE
  Mutations in the p53 tumor suppressor gene are one among the most common genetic abnormalities to be described in breast cancer. However, there are a few recant reports on non-viral vector-mediated p53 gene delivery in breast cancer.
  
  
  METHODS
  A new formulation of luminescent silica nanoparticles (LSNs) for gene delivery was produced by the two-step method with slight modification.
  
  
  RESULTS
  The pp53 plasmid constructs (p53-EGFP)/LSNs complexes were transfected into human breast cancer cell (MCF-7) and transfection efficiency was determined by FACS analysis. The gene expression was determined by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analysis respectively. Further the growth inhibition through induced apoptosis with pp53-EGFP/LSNs complex were assessed by trypan blue exclusion assay and annexin V staining, respectively. Interestingly the in vivo biodistribution of plasmid DNA study revealed the occurrence was investigated by PCR and RT-PCR. The transfection efficiency of LSNs showed the highest transfection efficiency among the LSN formulation was higher than that of commercially available Lipofectin®. The LSNs-mediated transfection of the p53 gene resulted in efficient high level of wild-type p53 mRNA and protein expression levels in MCF-7 cells. Selected tissues were analyzed for any potential toxicity by histological analysis the efficient reestablishment of wild-type p53 function in breast cancer cells restored the p53 dependent apoptotic pathway.
  
  
  CONCLUSIONS
  Taken together, our results reveal that cationic LSN-mediated p53 gene delivery may have potential application as a non-viral vector-mediated breast cancer gene therapy due to its effective induction of apoptosis and tumor growth inhibition.
authors.affiliation: Proteomics and Molecular Cell Physiology Lab, Department of Zoology, School of Life Sciences, Bharathiar University, Coimbatore, TN, IndiaDepartment of Radiation Oncology, King Hussein Cancer Center Jordan, Amman, Jordan.
authors.forename: Chandrababu
authors.initials: C
authors.lastname: Rejeeth
authors.affiliation: Proteomics and Molecular Cell Physiology Lab, Department of Zoology, School of Life Sciences, Bharathiar University, Coimbatore, TN, IndiaDepartment of Radiation Oncology, King Hussein Cancer Center Jordan, Amman, Jordan.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Salem
mesh_terms: D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics; D045744:Cell Line, Tumor; D002626:Chemistry, Pharmaceutical / Q000379:methods; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D049449:Luminescence; D049408:Luminescent Agents / Q000008:administration & dosage*; D061986:MCF-7 Cells; D053758:Nanoparticles / Q000008:administration & dosage*; D010957:Plasmids / Q000008:administration & dosage / Q000235:genetics; D012822:Silicon Dioxide / Q000008:administration & dosage*; D014018:Tissue Distribution / Q000502:physiology; D014162:Transfection / Q000379:methods; D016159:Tumor Suppressor Protein p53 / Q000008:administration & dosage* / Q000235:genetics
chemical_list: D049408:Luminescent Agents; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D012822:Silicon Dioxide
keywords: LSNs; breast cancer; nonviral vector; p53; pCMV