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

机译:基于金纳米棒的共价偶联轰击蛋白肽靶向的乳腺癌光热疗法

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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.
机译:光热疗法是一种用于杀死癌细胞的微创治疗方法,引起了人们的极大兴趣。为了提高治疗效果并减少副作用,光吸收剂对肿瘤的更好靶向已经成为抗癌的新概念。在这项研究中,使用Nanothinks酸作为链接,可以与所有胃泌素释放肽(GRP)受体亚型结合的蛙心素(BBN)类似物与金纳米棒(GNR)共价结合。 BBN类似物也涂有聚乙二醇,以增加其稳定性和生物相容性。通过紫外-可见和傅里叶变换红外光谱确认了相互作用。甲基噻唑四唑鎓测定未显示聚乙二醇化的GNR-BBN缀合物的细胞毒性。细胞结合和内在化研究显示,GNR-BBN-PEG共轭物对T47D细胞系的乳腺癌细胞具有高特异性和摄取率。体外研究显示暴露于新光热剂和连续波近红外激光照射的T47D细胞遭到破坏。生物分布研究表明缀合物在乳腺癌小鼠的肿瘤组织中大量积累。体内光热疗法在小鼠模型中显示了异种乳房癌的完全消失。

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