Tiwari Sanjay, Tirosh Boaz, Rubinstein Abraham
The Hebrew University of Jerusalem, Faculty of Medicine, School of Pharmacy Institute for Drug Research, P.O. Box 12065, Jerusalem, 91120, Israel.
The Hebrew University of Jerusalem, Faculty of Medicine, School of Pharmacy Institute for Drug Research, P.O. Box 12065, Jerusalem, 91120, Israel.
Int J Pharm. 2017 Oct 5;531(1):281-291. doi: 10.1016/j.ijpharm.2017.08.092. Epub 2017 Aug 24.
Nanoparticles of cationized polyacrylamide (CPAA NP), decorated with the recognition peptide VRPMPLQ (to produce CPAA-Pep NP), were prepared, characterized and tested biologically. They were designed to target dysplasia regions in the colon, characterized by overexpressed sialic acid. This targetability was augmented by the addition of VRPMPLQ. Their mean hydrodynamic size was 137nm with narrow size distribution and positive zeta potential. When incubated with three types of colon cancer cells, a 10-fold increase in the cell's uptake was found for the CPAA-Pep NP compared with the CPAA NP. The use of a scrambled sequence of the VRPMPLQ peptide and competition studies, employing excess of the free peptide verified the specific nature of the NP cellular uptake. Nanoparticles loaded with paclitaxel with and without VRPMPLQ indicated an improved pro-apoptotic activity of the CPAA-Pep NP. It is speculated that both positive charge and the presence of VRPMPLQ could serve as an improved strategy to deliver nanoparticles loaded with cytotoxic drugs for the treatment of colon cancer.
制备了用识别肽VRPMPLQ修饰的阳离子化聚丙烯酰胺纳米颗粒(CPAA-Pep NP),并对其进行了表征和生物学测试。它们旨在靶向结肠发育异常区域,该区域的特征是唾液酸过度表达。添加VRPMPLQ增强了这种靶向性。其平均流体动力学尺寸为137nm,尺寸分布窄,zeta电位为正。当与三种类型的结肠癌细胞孵育时,发现CPAA-Pep NP与CPAA NP相比,细胞摄取增加了10倍。使用VRPMPLQ肽的 scrambled序列以及采用过量游离肽的竞争研究证实了NP细胞摄取的特异性。负载有紫杉醇的含和不含VRPMPLQ的纳米颗粒表明CPAA-Pep NP的促凋亡活性有所提高。据推测,正电荷和VRPMPLQ的存在都可以作为一种改进的策略,用于递送负载细胞毒性药物的纳米颗粒来治疗结肠癌。