Université catholique de Louvain, Pharmaceutics and Drug Delivery, Louvain Drug Research Institute, Avenue E. Mounier, 73 B1 73 12, B-1200, Brussels, Belgium.
Mol Pharm. 2012 Nov 5;9(11):2961-73. doi: 10.1021/mp3002733. Epub 2012 Oct 4.
The integrin α(v)β(3) plays an important role in angiogenesis. It is expressed on tumoral endothelial cells as well as on some tumor cells. RGD peptides are well-known to bind preferentially to the α(v)β(3) integrin. In this context, targeting tumor cells or tumor vasculature by RGD-based strategies is a promising approach for delivering anticancer drugs or contrast agents for cancer therapy and diagnosis. RGD-based strategies include antagonist drugs (peptidic or peptidomimetic) of the RGD sequence, RGD-conjugates, and the grafting of the RGD peptide or peptidomimetic, as targeting ligand, at the surface of nanocarriers. Although all strategies are overviewed, this review aims to particularly highlight the position of RGD-based nanoparticles in cancer therapy and imaging. This review is divided into three parts: the first one describes the context of angiogenesis, the role of the integrin α(v)β(3), and the binding of the RGD peptide to this integrin; the second one focuses on RGD-based strategies in cancer therapy; while the third one focuses on RGD-based strategies in cancer diagnosis.
整合素 α(v)β(3) 在血管生成中起着重要作用。它不仅在肿瘤内皮细胞上表达，也在一些肿瘤细胞上表达。众所周知，RGD 肽优先与α(v)β(3)整合素结合。在这种情况下，通过基于 RGD 的策略靶向肿瘤细胞或肿瘤血管是一种很有前途的方法，可以将抗癌药物或对比剂递送至癌症治疗和诊断中。基于 RGD 的策略包括 RGD 序列的拮抗剂药物（肽或拟肽）、RGD 缀合物，以及将 RGD 肽或拟肽作为靶向配体接枝到纳米载体的表面。尽管所有策略都进行了综述，但本文旨在特别强调基于 RGD 的纳米颗粒在癌症治疗和成像中的地位。本文分为三个部分：第一部分描述了血管生成的背景、整合素α(v)β(3)的作用以及 RGD 肽与该整合素的结合；第二部分重点介绍了基于 RGD 的癌症治疗策略；第三部分则重点介绍了基于 RGD 的癌症诊断策略。
