EGFR-Targeted Hybrid Plasmonic Magnetic Nanoparticles Synergistically Induce Autophagy and Apoptosis in Non-Small Cell Lung Cancer CellsReport as inadecuate




EGFR-Targeted Hybrid Plasmonic Magnetic Nanoparticles Synergistically Induce Autophagy and Apoptosis in Non-Small Cell Lung Cancer Cells - Download this document for free, or read online. Document in PDF available to download.

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.

Methodology-Principal Findings

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-Significance

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.



Author: Tomohisa Yokoyama , Justina Tam , Shinji Kuroda, Ailing W. Scott, Jesse Aaron, Tim Larson, Manish Shanker, Arlene M. Correa, Seij

Source: http://plos.srce.hr/



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