Deci Michael B, Liu Maixian, Dinh Quoc Thai, Nguyen Juliane
Department of Pharmaceutical Sciences, School of Pharmacy, University at Buffalo, The State University of New York, Buffalo, New York.
Department of Experimental Pneumology and Allergology, Saarland University Faculty of Medicine, Homburg/Saar, Germany.
Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2018 Sep;10(5):e1511. doi: 10.1002/wnan.1511. Epub 2018 Feb 13.
Since their introduction in 1980, the number of advanced targeted nanocarrier systems has grown considerably. Nanocarriers capable of targeting single receptors, multiple receptors, or multiple epitopes have all been used to enhance delivery efficiency and selectivity. Despite tremendous progress, preclinical studies and clinically translatable nanotechnology remain disconnected. The disconnect in targeting efficacy may stem from poorly-understood factors such as receptor clustering, spatial control of targeting ligands, ligand mobility, and ligand architecture. Further, the relationship between receptor distribution and ligand architecture remains elusive. Traditionally, targeted nanocarriers were engineered assuming a "static" target. However, it is becoming increasingly clear that receptor expression patterns change in response to external stimuli and disease progression. Here, we discuss how cutting-edge technologies will enable a better characterization of the spatiotemporal distribution of membrane receptors and their clustering. We further describe how this will enable the design of new nanocarriers that selectively target the site of disease. Ultimately, we explore how the precision engineering of targeted nanocarriers that adapt to receptor dynamics will have the potential to drive nanotechnology to the forefront of therapy and make targeted nanomedicine a clinical reality. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Biology-Inspired Nanomaterials > Lipid-Based Structures Biology-Inspired Nanomaterials > Protein and Virus-Based Structures.
自1980年被引入以来，先进的靶向纳米载体系统数量大幅增长。能够靶向单个受体、多个受体或多个表位的纳米载体都已被用于提高递送效率和选择性。尽管取得了巨大进展，但临床前研究与可临床转化的纳米技术仍未接轨。靶向效能方面的脱节可能源于一些尚未被充分理解的因素，如受体聚集、靶向配体的空间控制、配体流动性和配体结构。此外，受体分布与配体结构之间的关系仍然难以捉摸。传统上，靶向纳米载体的设计是基于“静态”靶点。然而，越来越明显的是，受体表达模式会随着外部刺激和疾病进展而改变。在此，我们讨论前沿技术将如何更好地表征膜受体的时空分布及其聚集情况。我们还将描述这将如何促成新型纳米载体的设计，使其能够选择性地靶向疾病部位。最终，我们探讨适应受体动态变化的靶向纳米载体的精准工程如何有可能将纳米技术推向治疗前沿，并使靶向纳米医学成为临床现实。本文分类如下：治疗方法与药物发现＞新兴技术；纳米技术在生物学中的应用＞生物学中的纳米级系统；受生物学启发的纳米材料＞基于脂质的结构；受生物学启发的纳米材料＞基于蛋白质和病毒的结构。
