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基于共价偶联蛙皮素肽靶向的金纳米棒的乳腺癌光热疗法。

Breast cancer photothermal therapy based on gold nanorods targeted by covalently-coupled bombesin peptide.

作者信息

Heidari Zahra, Salouti Mojtaba, Sariri Reyhaneh

机构信息

Department of Biology, University of Guilan, Rasht, Iran. Department of Chemical and Biomolecular Engineering, Tulane University, New Orleans, Louisiana, USA.

出版信息

Nanotechnology. 2015 May 15;26(19):195101. doi: 10.1088/0957-4484/26/19/195101. Epub 2015 Apr 22.

Abstract

Photothermal therapy, a minimally invasive treatment method for killing cancers cells, has generated a great deal of interest. In an effort to improve treatment efficacy and reduce side effects, better targeting of photoabsorbers to tumors has become a new concept in the battle against cancer. In this study, a bombesin (BBN) analog that can bind to all gastrin-releasing peptide (GRP) receptor subtypes was bound covalently with gold nanorods (GNRs) using Nanothinks acid as a link. The BBN analog was also coated with poly(ethylene glycol) to increase its stability and biocompatibility. The interactions were confirmed by ultraviolet-visible and Fourier transform infrared spectroscopy. A methylthiazol tetrazolium assay showed no cytotoxicity of the PEGylated GNR-BBN conjugate. The cell binding and internalization studies showed high specificity and uptake of the GNR-BBN-PEG conjugate toward breast cancer cells of the T47D cell line. The in vitro study revealed destruction of the T47D cells exposed to the new photothermal agent combined with continuous-wave near-infrared laser irradiation. The biodistribution study showed significant accumulation of the conjugate in the tumor tissue of mice with breast cancer. The in vivo photothermal therapy showed the complete disappearance of xenographted breast tumors in the mouse model.

摘要

光热疗法是一种用于杀死癌细胞的微创治疗方法,已引起了广泛关注。为了提高治疗效果并减少副作用,使光吸收剂更好地靶向肿瘤已成为抗癌斗争中的一个新概念。在本研究中,一种能与所有胃泌素释放肽(GRP)受体亚型结合的蛙皮素(BBN)类似物,使用Nanothinks酸作为连接剂与金纳米棒(GNRs)共价结合。BBN类似物还用聚乙二醇进行了包被,以提高其稳定性和生物相容性。通过紫外可见光谱和傅里叶变换红外光谱证实了这种相互作用。甲基噻唑四氮唑试验表明聚乙二醇化的GNR-BBN偶联物没有细胞毒性。细胞结合和内化研究表明,GNR-BBN-PEG偶联物对T47D细胞系的乳腺癌细胞具有高度特异性和摄取能力。体外研究显示,在连续波近红外激光照射下,暴露于这种新型光热剂的T47D细胞遭到破坏。生物分布研究表明,该偶联物在患有乳腺癌的小鼠肿瘤组织中大量蓄积。体内光热疗法显示,在小鼠模型中,移植的乳腺肿瘤完全消失。

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