Tseng Ching-Li, Wu Steven Yueh-Hsiu, Wang Wen-Hsi, Peng Cheng-Liang, Lin Feng-Huei, Lin Chien-Cheng, Young Tai-Horng, Shieh Ming-Jium
Institute of Biomedical Engineering, National Taiwan University, Taipei 100, Taiwan, ROC.
Biomaterials. 2008 Jul;29(20):3014-22. doi: 10.1016/j.biomaterials.2008.03.033. Epub 2008 Apr 23.
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.
肺癌是当今最具恶性的癌症;为了开发一种用于肺癌治疗的有效药物递送系统,用中性抗生物素蛋白(异硫氰酸荧光素)-生物素化表皮生长因子(EGF)修饰明胶纳米颗粒(GPs),以形成靶向表皮生长因子受体(EGFR)的纳米颗粒(GP-Av-bEGF)。通过雾化器产生GP-Av-bEGF的气溶胶液滴,并通过气溶胶递送将其递送至肺癌小鼠模型。对气溶胶大小的分析表明,雾化后99%的纳米颗粒的质量中值空气动力学直径(MMAD)在适合下呼吸道沉积的范围内(0.5-5微米)。通过肺水肿和髓过氧化物酶(MPO)活性测定来检查吸入纳米颗粒的安全性。未发现吸入后有急性肺部炎症的迹象。从活小鼠获得的荧光图像显示,GP-Av-bEGF能够以更特异的方式靶向癌肺。对器官的荧光分析表明,GP-Av-bEGF主要分布在癌肺中。相比之下,正常肺中的纳米颗粒积累较少。组织学结果表明,由于EGFR结合,荧光GP-Av-bEGF与抗EGFR免疫染色共定位。这项研究的结果表明,GP-Av-bEGF在体内能够靶向EGFR过表达的癌细胞,并且通过简单的气溶胶递送给药时可能被证明是有益的药物载体,可用于治疗肺癌。