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The Choice of Targets and Ligands for Site-Specific Delivery of Nanomedicine to Atherosclerosis.
Cardiovascular Research ( IF 10.2 ) Pub Date : 2020-02-20 , DOI: 10.1093/cvr/cvaa047
Adil Zia 1 , Yuao Wu 1, 2 , Tuan Nguyen 3 , Xiaowei Wang 4 , Karlheinz Peter 4 , Hang T Ta 1, 2
Affiliation  

As nanotechnologies advance into clinical medicine, novel methods for applying nanomedicine to cardiovascular diseases are emerging. Extensive research has been undertaken to unlock the complex pathogenesis of atherosclerosis. However, this complexity presents challenges to develop effective imaging and therapeutic modalities for early diagnosis and acute intervention. The choice of ligand-receptor system vastly influences the effectiveness of nanomedicine. This review collates current ligand-receptor systems used in targeting functionalized nanoparticles for diagnosis and treatment of atherosclerosis. Our focus is on the binding affinity and selectivity of ligand-receptor systems, as well as the relative abundance of targets throughout the development and progression of atherosclerosis. Antibody-based targeting systems are currently the most commonly researched due to their high binding affinities when compared with other ligands, such as antibody fragments, peptides, and other small molecules. However, antibodies tend to be immunogenic due to their size. Engineering antibody fragments can address this issue but will compromise their binding affinity. Peptides are promising ligands due to their synthetic flexibility and low production costs. Alongside the aforementioned binding affinity of ligands, the choice of target and its abundance throughout distinct stages of atherosclerosis and thrombosis is relevant to the intended purpose of the nanomedicine. Further studies to investigate the components of atherosclerotic plaques are required as their cellular and molecular profile shifts over time.

中文翻译:

将纳米药物定点输送到动脉粥样硬化的靶标和配体的选择。

随着纳米技术进入临床医学,将纳米医学应用于心血管疾病的新方法不断涌现。已经进行了广泛的研究以解开动脉粥样硬化的复杂发病机制。然而,这种复杂性对开发用于早期诊断和急性干预的有效成像和治疗方式提出了挑战。配体-受体系统的选择极大地影响了纳米医学的有效性。这篇综述整理了当前用于靶向功能化纳米粒子以诊断和治疗动脉粥样硬化的配体-受体系统。我们的重点是配体-受体系统的结合亲和力和选择性,以及动脉粥样硬化发展和进展过程中靶标的相对丰度。与其他配体(如抗体片段、肽和其他小分子)相比,基于抗体的靶向系统由于其高结合亲和力而成为目前研究最多的系统。然而,由于它们的大小,抗体往往具有免疫原性。工程抗体片段可以解决这个问题,但会影响它们的结合亲和力。由于其合成灵活性和低生产成本,肽是有前途的配体。除了上述配体的结合亲和力外,在动脉粥样硬化和血栓形成的不同阶段,靶标的选择及其丰度与纳米药物的预期目的有关。需要进一步研究动脉粥样硬化斑块的成分,因为它们的细胞和分子特征会随着时间的推移而变化。
更新日期:2020-02-20
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