Zia Adil, Wu Yuao, Nguyen Tuan, Wang Xiaowei, Peter Karlheinz, Ta Hang T
Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, QLD 4072, Australia.
School of Pharmacy, Pharmacy Australia Centre of Excellence, The University of Queensland, Woolloongabba, QLD 4102, Australia.
Cardiovasc Res. 2020 Nov 1;116(13):2055-2068. doi: 10.1093/cvr/cvaa047.
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.
随着纳米技术在临床医学中的发展，将纳米医学应用于心血管疾病的新方法不断涌现。人们已经进行了广泛的研究来揭示动脉粥样硬化的复杂发病机制。然而，这种复杂性给开发用于早期诊断和急性干预的有效成像和治疗方式带来了挑战。配体-受体系统的选择对纳米医学的有效性有很大影响。本综述整理了目前用于靶向功能化纳米颗粒以诊断和治疗动脉粥样硬化的配体-受体系统。我们关注的是配体-受体系统的结合亲和力和选择性，以及在动脉粥样硬化发展和进展过程中靶点的相对丰度。基于抗体的靶向系统由于与其他配体（如抗体片段、肽和其他小分子）相比具有较高的结合亲和力，目前是研究最广泛的。然而，抗体因其大小往往具有免疫原性。改造抗体片段可以解决这个问题，但会降低它们的结合亲和力。肽由于其合成灵活性和低成本，是很有前景的配体。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，靶点的选择及其丰度与纳米医学的预期用途相关。由于动脉粥样硬化斑块的细胞和分子特征会随时间变化，因此需要进一步研究来调查其组成成分。
