Li Dandan, Chen Xin, Wang Hong, Liu Jie, Zheng Meiling, Fu Yang, Yu Yuan, Zhi Jinfang
Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, 100190, PR China.
University of Chinese Academy of Sciences, 100049, PR China.
J Biophotonics. 2017 Dec;10(12):1636-1646. doi: 10.1002/jbio.201700011. Epub 2017 Jun 21.
In this study, a multicomponent nanodiamonds (NDs)-based targeting drug delivery system, cetuximab-NDs-cisplatin bioconjugate, combining both specific targeting and enhanced therapeutic efficacy capabilities, is developed and characterized. The specific targeting ability of cetuximab-NDs-cisplatin system on human liver hepatocellular carcinoma (HepG2) cells is evaluated through epidermal growth factor receptor (EGFR) blocking experiments, since EGFR is over-expressed on HepG2 cell membrane. Besides, cytotoxic evaluation confirms that cetuximab-NDs-cisplatin system could significantly inhibit the growth of HepG2 cells, and the therapeutic activity of this system is proven to be better than that of both nonspecific NDs-cisplatin conjugate and specific EGF-NDs-cisplatin conjugate. Furthermore, a 3-dimensional (3D) Raman imaging technique is utilized to visualize the targeting efficacy and enhanced internalization of cetuximab-NDs-cisplatin system in HepG2 cells, using the NDs existing in the bioconjugate as Raman probes, based on the characteristic Raman signal of NDs at 1332 cm . These advantageous properties of cetuximab-NDs-cisplatin system propose a prospective imaging and treatment tool for further diagnostic and therapeutic purposes.
在本研究中,开发并表征了一种基于多组分纳米金刚石(NDs)的靶向给药系统,即西妥昔单抗-NDs-顺铂生物共轭物,该系统兼具特异性靶向和增强治疗效果的能力。由于表皮生长因子受体(EGFR)在人肝癌(HepG2)细胞膜上过度表达,通过EGFR阻断实验评估了西妥昔单抗-NDs-顺铂系统对HepG2细胞的特异性靶向能力。此外,细胞毒性评估证实西妥昔单抗-NDs-顺铂系统可显著抑制HepG2细胞的生长,且该系统的治疗活性被证明优于非特异性NDs-顺铂共轭物和特异性EGF-NDs-顺铂共轭物。此外,利用三维(3D)拉曼成像技术,基于生物共轭物中存在的NDs在1332 cm处的特征拉曼信号,将其作为拉曼探针,以可视化西妥昔单抗-NDs-顺铂系统在HepG2细胞中的靶向效果和增强的内化作用。西妥昔单抗-NDs-顺铂系统的这些有利特性为进一步的诊断和治疗目的提供了一种前瞻性的成像和治疗工具。