Targeting efficiency and biodistribution of biotinylated-EGF-conjugated gelatin nanoparticles administered via aerosol delivery in nude mice with lung cancer.
Lung cancer is the most malignant cancer today; in order to develop an effective drug delivery system for lung cancer therapy, gelatin nanoparticles (GPs) were modified with NeutrAvidin(FITC)-biotinylated epidermal growth factor (EGF) to form EGF receptor (EGFR)-seeking nanoparticles (GP-Av-bEGF). Aerosol droplets of the GP-Av-bEGF were generated by using a nebulizer and were delivered to mice model of lung cancer via aerosol delivery. Analysis of the aerosol size revealed that 99% of the nanoparticles after nebulization had a mass median aerodynamic diameter (MMAD) within the suitable range (0.5-5 microm) for lower airway deposition. The safety of inhaled nanoparticles was examined by lung edema and myeloperoxidase (MPO) activity assay. There's no finding suggestive of acute lung inflammation following inhalation. The fluorescence images obtained from live mice showed that the GP-Av-bEGF could target the cancerous lungs in a more specific manner. Fluorescence analysis of the organs revealed that the GP-Av-bEGF was mainly distributed in cancerous lungs. In contrast, nanoparticle accumulation was lower in normal lungs. The histological results indicated that the fluorescent GP-Av-bEGF was colocalized with the anti-EGFR-immunostain due to EGFR binding. The results of this study revealed that GP-Av-bEGF could target to the EGFR-overexpression cancer cells in vivo and may prove to be beneficial drug carriers when administered by simple aerosol delivery for the treatment of lung cancer.
Tseng
Ching-Li
CL
Institute of Biomedical Engineering, National Taiwan University, Taipei 100, Taiwan, ROC.
Wu
Steven Yueh-Hsiu
SY
Wang
Wen-Hsi
WH
Peng
Cheng-Liang
CL
Lin
Feng-Huei
FH
Lin
Chien-Cheng
CC
Young
Tai-Horng
TH
Shieh
Ming-Jium
MJ
D000336:Aerosols; D000818:Animals; D001710:Biotin / Q000378:metabolism*; D004815:Epidermal Growth Factor / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005780:Gelatin / Q000737:chemistry*; D008175:Lung Neoplasms / Q000378:metabolism*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008855:Microscopy, Electron, Scanning; D053758:Nanoparticles; D014018:Tissue Distribution
D000336:Aerosols; D004815:Epidermal Growth Factor; D001710:Biotin; D005780:Gelatin