Hall Sejal S, Mitragotri Samir, Daugherty Patrick S
Department of Chemical Engineering, University of California, Santa Barbara, California 93106, USA.
Biotechnol Prog. 2007 May-Jun;23(3):749-54. doi: 10.1021/bp060333l. Epub 2007 May 1.
Peptide ligands capable of mediating nanoparticle adhesion to human red blood cells (RBCs) were identified from a large bacterial display peptide library. Peptides were displayed on the surface of fluorescent Escherichia coli, enabling quantitative measurement of RBC binding and high-throughput screening using fluorescence-activated cell sorting. One of the isolated clones remained attached to RBCs under high-shear stresses equivalent to those encountered in vivo. Furthermore, nanoparticles functionalized with the identified RBC-binding peptides exhibited nearly 100-fold increased RBC binding relative to nonfunctionalized particles in the presence of physiologically relevant concentrations of human serum albumin, indicating that peptides remained functional in the absence of the protein scaffold used for display. The RBC-binding peptides identified here provide new opportunities for sustained therapeutic delivery applications whereby nanoparticulate drug carriers can be attached to RBCs to achieve long-circulating carrier systems.
从一个大型细菌展示肽库中鉴定出了能够介导纳米颗粒与人红细胞(RBC)粘附的肽配体。肽展示在荧光大肠杆菌表面,可通过荧光激活细胞分选对红细胞结合进行定量测量并进行高通量筛选。其中一个分离的克隆在相当于体内所遇的高剪切应力下仍能附着于红细胞。此外,在生理相关浓度的人血清白蛋白存在下,用鉴定出的红细胞结合肽功能化的纳米颗粒相对于未功能化的颗粒表现出近100倍的红细胞结合增加,这表明肽在没有用于展示的蛋白质支架的情况下仍保持功能。这里鉴定出的红细胞结合肽为持续治疗递送应用提供了新机会,由此纳米颗粒药物载体可附着于红细胞以实现长循环载体系统。