Ben-Arie Noa, Kedmi Ranit, Peer Dan
Laboratory of Nanomedicine, Department of Cell Research and Immunology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel.
Methods Mol Biol. 2012;757:497-507. doi: 10.1007/978-1-61779-166-6_29.
Integrins are heterodimeric membrane glycoproteins composed of noncovalently associated α and β subunits. Integrins support cell attachment and migration on the surrounding extracellular matrix as well as mediate cell-cell interaction in physiological and pathological settings. Constant recycling of integrins from the plasma membrane to the endosome makes integrins ideal receptors for the delivery of drugs to the cell cytoplasm. RNA interference (RNAi) has evolved not only as a powerful tool for studying gene expression and validating new drug targets, but also as a potential therapeutic intervention. However, the major challenge facing the translation of RNAi into clinical practice is the lack of efficient systemic delivery to specific cell types. Utilizing integrins as delivery target, we have recently devised a strategy to target leukocytes termed Integrin-targeted and stabilized NanoParticles (I-tsNPs) that entrap high RNAi payloads and deliver them in a leukocyte-specific manner to induce robust gene silencing.
整合素是由非共价结合的α和β亚基组成的异二聚体膜糖蛋白。整合素支持细胞在周围细胞外基质上的附着和迁移，并在生理和病理环境中介导细胞间相互作用。整合素从质膜到内体的持续循环使整合素成为将药物递送至细胞质的理想受体。RNA干扰（RNAi）不仅已发展成为研究基因表达和验证新药物靶点的强大工具，而且还是一种潜在的治疗干预手段。然而，将RNAi转化为临床实践面临的主要挑战是缺乏对特定细胞类型的有效全身递送。利用整合素作为递送靶点，我们最近设计了一种靶向白细胞的策略，称为整合素靶向稳定纳米颗粒（I-tsNPs），它能捕获高含量的RNAi，并以白细胞特异性方式递送，以诱导强烈的基因沉默。
