Artificial Internalizing Receptors: Intracellular Delivery of Cargo Through Bio-Orthogonal Recognition.
Søgaard, A. B., Hansson, R. F., Tvilum, A. S., Zelikin, A. N., Artificial Internalizing Receptors: Intracellular Delivery of Cargo Through Bio-Orthogonal Recognition. Adv. Healthcare. Mater. 2024, 2402472.
DOI: https://doi.org/10.1002/adhm.202402472
Abstract
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.
