School of Biotechnology, Kalinga Institute of Industrial Technology Deemed to be University, Campus 11, Patia, Bhubaneswar, Odisha 751024, India.
Conversion & Catalysis Division, CSIR-Indian Institute of Petroleum, Dehradun 248005, India.
Int J Pharm. 2019 May 30;563:198-207. doi: 10.1016/j.ijpharm.2019.04.007. Epub 2019 Apr 3.
Based on the cell penetrating ability of tryptophan-containing peptides, eight linear hexapeptides have been designed, synthesized and explored their efficiency toward the synthesis of gold nanoparticles under sunlight. The peptide generated gold nanoparticles (LP-GNPs) have been characterized by UV-visible spectroscopy, Transmission Electron Microscopy (TEM) and Dynamic Light Scattering (DLS) techniques. The binding ability of LP-GNPs toward siRNA, evaluated by gel electrophoresis indicates that sequence-selective-GNPs without any surface modifications exhibit strong affinity toward negatively charged biomolecules. Cellular uptake studies suggest that LP-GNPs exhibit significant uptake of fluorescence-labeled siRNA inside the cells as evidenced from Fluorescence Microscopy. In vitro gene silencing efficiency using newly generated GNPs revealed that above mentioned LP-GNPs efficiently down-regulate the level of GAPGH gene in colon cancer cells. Comparative gene silencing efficiency results indicate that anisotropic LP7-GNPs exhibit comparable efficacy to other existing carrier systems, such as Lipofectamine 2000 in presence of serum, mimicking in-vivo system. In conclusion, our results demonstrate that peptide-GNPs based delivery system for siRNA emerges to be effective to deliver RNAi therapeutics, uncovering new avenue in oncotherapy.
基于色氨酸肽的细胞穿透能力,设计、合成了 8 条线性六肽,并探索了它们在阳光照射下合成金纳米粒子的效率。肽生成的金纳米粒子(LP-GNPs)通过紫外-可见光谱、透射电子显微镜(TEM)和动态光散射(DLS)技术进行了表征。通过凝胶电泳评估 LP-GNPs 对 siRNA 的结合能力表明,未经任何表面修饰的序列选择性-GNPs 对带负电荷的生物分子具有很强的亲和力。细胞摄取研究表明,LP-GNPs 在内皮细胞内表现出对荧光标记 siRNA 的显著摄取,荧光显微镜证实了这一点。使用新生成的 GNPs 进行体外基因沉默效率研究表明,上述 LP-GNPs 可有效下调结肠癌细胞中 GAPGH 基因的水平。比较基因沉默效率的结果表明,各向异性的 LP7-GNPs 在存在血清的情况下与其他现有载体系统(如 Lipofectamine 2000)具有相当的功效,模拟了体内系统。总之,我们的结果表明,基于肽-GNPs 的 siRNA 传递系统在传递 RNAi 治疗方面是有效的,为肿瘤治疗开辟了新途径。