Søgaard Ane Bretschneider, Hansson Rikke Fabech, Tvilum Anne Selch, Zelikin Alexander N
iNano Interdisciplinary Nanoscience Center, Aarhus University, Aarhus, 8000, Denmark.
Department of Chemistry, Aarhus University, Aarhus, 8000, Denmark.
Adv Healthc Mater. 2024 Dec;13(32):e2402472. doi: 10.1002/adhm.202402472. Epub 2024 Oct 21.
Drug targeting is a methodology that helps to overcome the side effects of therapeutic molecules. However, insufficient targeting specificity and the on-target/off-site delivery leave much room for improvement in the targeting endeavors. One approach to enhance the specificity of drug targeting is to engineer artificial receptors with recognition ligands not observed in nature. To this end, artificial internalizing receptors that feature cholesterylamine as the artificial pull-in mechanism, and an anti-fluorescein antibody as the exofacial recognition and capture tool are developed. Fluorescein labeling is among the most routine techniques in biochemistry and can readily provide a way to make cognate derivatives for receptor-mediated endocytosis using these artificial receptors. Herein, the synthesis and the structure-activity relationship for these artificial receptors are detailed, their potency and efficacy in mediating drug delivery for the antibody-drug conjugates are illustrated, and the scope and limitations of targeting the chemically engineered cells via artificial receptors are investigated. Taken together, the presented data explore an innovative approach to drug targeting and contribute to the development of techniques in cell engineering using the tools of chemistry.
药物靶向是一种有助于克服治疗性分子副作用的方法。然而，靶向特异性不足以及靶上/靶外递送使得靶向研究仍有很大的改进空间。增强药物靶向特异性的一种方法是设计具有自然界中未观察到的识别配体的人工受体。为此，开发了以胆固醇胺作为人工引入机制、以抗荧光素抗体作为外表面识别和捕获工具的人工内化受体。荧光素标记是生物化学中最常规的技术之一，并且可以很容易地提供一种使用这些人工受体来制备用于受体介导的内吞作用的同源衍生物的方法。本文详细介绍了这些人工受体的合成及其构效关系，阐述了它们在介导抗体-药物偶联物药物递送方面的效力和功效，并研究了通过人工受体靶向化学工程细胞的范围和局限性。综上所述，所呈现的数据探索了一种创新的药物靶向方法，并有助于利用化学工具开发细胞工程技术。
