Targeting efficiency and biodistribution of biotinylated-EGF-conjugated gelatin nanoparticles administered via aerosol delivery in nude mice with lung cancer

被引：128

作者：

Tseng, Ching-Li ^{[1
]}

Wu, Steven Yueh-Hsiu ^{[1
]}

Wang, Wen-Hsi ^{[1
]}

Peng, Cheng-Liang ^{[1
]}

Lin, Feng-Huei ^{[1
]}

Lin, Chien-Cheng ^{[1
]}

Young, Tai-Horng ^{[1
]}

Shieh, Ming-Jium ^{[1
]}

机构：

[1] Natl Taiwan Univ, Inst Biomed Engn, Taipei 100, Taiwan

来源：

BIOMATERIALS | 2008年 / 29卷 / 20期

关键词：

nanoparticle; gelatin; in vivo test; lung cancer; drug delivery; EGF;

D O I：

10.1016/j.biomaterials.2008.03.033

中图分类号：

R318 [生物医学工程];

学科分类号：

0831 ;

摘要：

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 mu m) 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. (C) 2008 Elsevier Ltd. All rights reserved.

引用

页码：3014 / 3022

页数：9

共 37 条

[1]

Carlsson J, 1999, ACTA ONCOL, V38, P313

[2]

Coester CJ, 2000, J MICROENCAPSUL, V17, P187

[3] Carrier-based strategies for targeting protein and peptide drugs to the lungs [J].

Cryan, SA .

AAPS JOURNAL, 2005, 7 (01) :E20-E41

[4] Investigation of the proinflammatory potential of biodegradable nanoparticle drug delivery systems in the lung [J].

Dailey, L. A. ;

Jekel, N. ;

Fink, L. ;

Gessler, T. ;

Schmehl, T. ;

Wittmar, M. ;

Kissel, T. ;

Seeger, W. .

TOXICOLOGY AND APPLIED PHARMACOLOGY, 2006, 215 (01) :100-108

[5]

DALBY R, 1996, INHALATION AEROSOLS

[6] Generation of gelatin aerosol particles from nebulized solutions as model drug carrier systems [J].

Deaton, AT ;

Jones, LD ;

Dunbar, CA ;

Hickey, AJ ;

Williams, DM .

PHARMACEUTICAL DEVELOPMENT AND TECHNOLOGY, 2002, 7 (02) :147-153

[7]

FAN Z, 1994, J BIOL CHEM, V269, P27595

[8] The effect of anti-inflammatory properties of mycophenolate mofetil on the development of lung reperfusion injury [J].

Farivar, AS ;

MacKinnon-Patterson, B ;

Barnes, AD ;

Mulligan, MS .

JOURNAL OF HEART AND LUNG TRANSPLANTATION, 2005, 24 (12) :2235-2242

[9] In vitro study of the pulmonary translocation of nanoparticles - A preliminary study [J].

Geys, J ;

Coenegrachts, L ;

Vercammen, J ;

Engelborghs, Y ;

Nemmar, A ;

Nemery, B ;

Hoet, PHM .

TOXICOLOGY LETTERS, 2006, 160 (03) :218-226

[10]

Guyton AC., 2006, Textbook of Medical Physiology, V11th edn.

← 1 2 3 4 →