Rationally Designed Multivalent Aptamers Targeting Cell Surface for Biomedical Applications
Rationally Designed Multivalent Aptamers Targeting Cell Surface for Biomedical Applications
复制标题
合理设计的靶向细胞表面的多价适体用于生物医学应用
DOI：
10.1021/acsami.0c15644
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发表时间：
2021-03-03
影响因子：
9.5
通讯作者：
Xia, Fan
中科院分区：
文献类型：
--
作者：
Lin, Meihua;Zhang, Jian;Xia, Fan
细胞表面配体和受体之间的特异性相互作用在细胞生物学过程中起着重要作用。核酸适体作为常用的配体能够特异性识别并与膜蛋白受体紧密结合以调节细胞命运。因此，具有适体的分子探针可以通过靶向癌细胞的过表达膜蛋白而应用于癌症诊断和靶向治疗。然而，由于其在体内快速降解和快速肾小球清除，适体在生理条件下的应用仍然面临挑战。受天然多价相互作用的启发，已经开发了许多方法来构建多价适体，以提高适体在复杂基质中的性能，具有更高的结合亲和力、更高的稳定性和更长的循环时间。本文首先介绍了基于蛋白质的SELEX和基于全细胞的SELEX用于靶向细胞表面的适体的产生。然后，我们强调的方法来制造多价适体，并讨论其性质。通过将不同的材料（包括无机纳米材料、二酰基脂质、聚合物纳米颗粒和DNA纳米结构）作为支架与界面修饰技术相结合，我们总结了四种多价适体。在此之后，在生物传感和靶向治疗的代表性应用程序进行了说明，以显示多价适体的性能提高。此外，我们分析了多价适体的临床实践的挑战和机遇。
Specific interactions between ligands and receptors on cell surface play an important role in the cell biological process. Nucleic acid aptamers as commonly used ligands enable specific recognition and tight binding to membrane protein receptors for modulation of cell fate. Therefore, molecular probes with aptamers can be applied for cancer diagnosis and targeted therapy by targeting overexpression membrane proteins of cancer cells. However, because of their fast degradation and rapid glomerulus clearance in vivo, the applications of aptamers in physiological conditions remain challenged. Inspired by natural multivalent interactions, many approaches have been developed to construct multivalent aptamers to improve the performance of aptamers in complex matrices with higher binding affinity, more stability, and longer circulation time. In this review, we first introduce the aptamer generation from purified protein-based SELEX and whole cell-based SELEX for targeting the cell surface. We then highlight the approaches to fabricate multivalent aptamers and discuss their properties. By integrating different materials (including inorganic nanomaterials, diacyllipid, polymeric nanoparticles, and DNA nanostructures) as scaffolds with an interface modification technique, we have summarized four kinds of multivalent aptamers. After that, representative applications in biosensing and targeted therapy are illustrated to show the elevated performance of multivalent aptamers. In addition, we analyze the challenges and opportunities for the clinical practices of multivalent aptamers.