Investigating the specific uptake of EGF-conjugated nanoparticles in lung cancer cells using fluorescence imaging

Cancer Nanotechnology

Original Paper

Zhihong Zhang¹  Juan Chen²  Lili Ding²  Weiguo Cao³  Honglin Jin⁴  Gang Zheng⁵  Jonathan F. Lovell⁶  Kenneth Ng⁶ 

[1] Britton Chance Center for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics–Huazhong University of Science and Technology, Wuhan, China;Ontario Cancer Institute and Campbell Family Cancer Research Institute, University of Toronto, Toronto, Canada;Ontario Cancer Institute and Campbell Family Cancer Research Institute, University of Toronto, Toronto, Canada;Department of Medical Biophysics, University of Toronto, Toronto, Canada;Ontario Cancer Institute and Campbell Family Cancer Research Institute, University of Toronto, Toronto, Canada;Department of Medical Biophysics, University of Toronto, Toronto, Canada;Britton Chance Center for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics–Huazhong University of Science and Technology, Wuhan, China;Ontario Cancer Institute and Campbell Family Cancer Research Institute, University of Toronto, Toronto, Canada;Department of Medical Biophysics, University of Toronto, Toronto, Canada;Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Canada;Ontario Cancer Institute and Campbell Family Cancer Research Institute, University of Toronto, Toronto, Canada;Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Canada;

关键词: Nanoparticles;    GFP;    EGF;    Lung cancer;    Targeting specificity;   

DOI  :  10.1007/s12645-010-0009-x

 received in 2010-10-15, accepted in 2010-10-27,  发布年份 2010

来源: Springer

【 摘 要 】

Targeted nanoparticles have the potential to deliver a large drug payload specifically to cancer cells. Targeting requires that a ligand on the nanoparticle surface interact with a specific membrane receptor on target cells. However, the contribution of the targeting ligand to nanoparticle delivery is often influenced by non-specific nanoparticle uptake or secondary targeting mechanisms. In this study, we investigate the epidermal growth factor (EGF) receptor-targeting specificity of a nanoparticle by dual-color fluorescent labeling. The targeted nanoparticle was a fluorescently labeled, EGF-conjugated HDL-like peptide–phospholipid scaffold (HPPS) and the cell lines expressed EGF receptor linked with green fluorescent protein (EGFR-GFP). Using LDLA7 cells partially expressing EGFR-GFP, fluorescence imaging demonstrated the co-internalization of EGFR-GFP and EGF-HPPS, thus validating its targeting specificity. Furthermore, specific EGFR-mediated uptake of the EGF-HPPS nanoparticle was confirmed using human non-small cell lung cancer A549 cells. Subsequent confocal microscopy and flow cytometry studies delineated how secondary targeting mechanisms affected the EGFR targeting. Together, this study confirms the EGFR targeting of EGF-HPPS in lung cancer cells and provides insight on the potential influence of unintended targets on the desired ligand–receptor interaction.

【 授权许可】

Unknown   
© Springer-Verlag 2010