title: EGFR-targeted hybrid plasmonic magnetic nanoparticles synergistically induce autophagy and apoptosis in non-small cell lung cancer cells.
abstract: BACKGROUND
  The epidermal growth factor receptor (EGFR) is overexpressed in 80% of non-small cell lung cancer (NSCLC) and is associated with poor survival. In recent years, EGFR-targeted inhibitors have been tested in the clinic for NSCLC. Despite the emergence of novel therapeutics and their application in cancer therapy, the overall survival rate of lung cancer patients remains 15%. To develop more effective therapies for lung cancer we have combined the anti-EGFR antibody (Clone 225) as a molecular therapeutic with hybrid plasmonic magnetic nanoparticles (NP) and tested on non-small cell lung cancer (NSCLC) cells.
  
  
  RESULTS
  Cell viability was determined by trypan-blue assay. Cellular protein expression was determined by Western blotting. C225-NPs were detected by electron microscopy and confocal microscopy, and EGFR expression using immunocytochemistry. C225-NP exhibited a strong and selective antitumor effect on EGFR-expressing NSCLC cells by inhibiting EGFR-mediated signal transduction and induced autophagy and apoptosis in tumor cells. Optical images showed specificity of interactions between C225-NP and EGFR-expressing NSCLC cells. No binding of C225-NP was observed for EGFR-null NSCLC cells. C225-NP exhibited higher efficiency in induction of cell killing in comparison with the same amount of free C225 antibody in tumor cells with different levels of EGFR expression. Furthermore, in contrast to C225-NP, free C225 antibody did not induce autophagy in cells. However, the therapeutic efficacy of C225-NP gradually approached the level of free antibodies as the amount of C225 antibody conjugated per nanoparticle was decreased. Finally, attaching C225 to NP was important for producing the enhanced tumor cell killing as addition of mixture of free C225 and NP did not demonstrate the same degree of cell killing activity.
  
  
  CONCLUSIONS
  We demonstrated for the first time the molecular mechanism of C225-NP induced cytotoxic effects in lung cancer cells that are not characteristic for free molecular therapeutics thus increasing efficacy of therapy against NSCLC.
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, United States of America.
authors.forename: Tomohisa
authors.initials: T
authors.lastname: Yokoyama
authors.forename: Justina
authors.initials: J
authors.lastname: Tam
authors.forename: Shinji
authors.initials: S
authors.lastname: Kuroda
authors.forename: Ailing W
authors.initials: AW
authors.lastname: Scott
authors.forename: Jesse
authors.initials: J
authors.lastname: Aaron
authors.forename: Tim
authors.initials: T
authors.lastname: Larson
authors.forename: Manish
authors.initials: M
authors.lastname: Shanker
authors.forename: Arlene M
authors.initials: AM
authors.lastname: Correa
authors.forename: Seiji
authors.initials: S
authors.lastname: Kondo
authors.forename: Jack A
authors.initials: JA
authors.lastname: Roth
authors.forename: Konstantin
authors.initials: K
authors.lastname: Sokolov
authors.forename: Rajagopal
authors.initials: R
authors.lastname: Ramesh
mesh_terms: D000912:Antibodies, Neoplasm / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D004353:Drug Evaluation, Preclinical; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D006801:Humans; D058185:Magnetite Nanoparticles / Q000627:therapeutic use*; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors
chemical_list: D000912:Antibodies, Neoplasm; D058185:Magnetite Nanoparticles; D009363:Neoplasm Proteins; C512478:EGFR protein, human; D066246:ErbB Receptors
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