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用整合素靶向纳米药物调节血管生成。

Modulating angiogenesis with integrin-targeted nanomedicines.

机构信息

Centro de Investigación Príncipe Felipe, Polymer Therapeutics Lab., Av. Eduardo Primo Yúfera 3, E-46012 Valencia, Spain.

出版信息

Adv Drug Deliv Rev. 2017 Sep 15;119:101-119. doi: 10.1016/j.addr.2017.05.008. Epub 2017 May 12.

Abstract

Targeting angiogenesis-related pathologies, which include tumorigenesis and metastatic processes, has become an attractive strategy for the development of efficient guided nanomedicines. In this respect, integrins are cell-adhesion molecules involved in angiogenesis signaling pathways and are overexpressed in many angiogenic processes. Therefore, they represent specific biomarkers not only to monitor disease progression but also to rationally design targeted nanomedicines. Arginine-glycine-aspartic (RGD) containing peptides that bind to specific integrins have been widely utilized to provide ligand-mediated targeting capabilities to small molecules, peptides, proteins, and antibodies, as well as to drug/imaging agent-containing nanomedicines, with the final aim of maximizing their therapeutic index. Within this review, we aim to cover recent and relevant examples of different integrin-assisted nanosystems including polymeric nanoconstructs, liposomes, and inorganic nanoparticles applied in drug/gene therapy as well as imaging and theranostics. We will also critically address the overall benefits of integrin-targeting.

摘要

针对血管生成相关病变(包括肿瘤发生和转移过程)已成为开发高效导向纳米药物的一种有吸引力的策略。在这方面,整合素是参与血管生成信号通路的细胞粘附分子,在许多血管生成过程中过度表达。因此,它们不仅是监测疾病进展的特异性生物标志物,也是合理设计靶向纳米药物的标志物。含有精氨酸-甘氨酸-天冬氨酸(RGD)的肽与特定的整合素结合,已被广泛用于为小分子、肽、蛋白质和抗体以及含有药物/成像剂的纳米药物提供配体介导的靶向能力,最终目的是最大限度地提高其治疗指数。在这篇综述中,我们旨在涵盖不同整合素辅助纳米系统的最新和相关实例,包括聚合物纳米结构、脂质体和无机纳米粒子,这些系统应用于药物/基因治疗以及成像和治疗学。我们还将批判性地讨论整合素靶向的整体益处。

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