Sung, Yejin Choi, Youngjin Kim, Eun Sun Ryu, Ju Hee Kwon, Ick Chan 2025-03-22T12:30:24Z 2025-03-22T12:30:24Z 2025-03-19 2025-04 0168-3659 https://pubs.kist.re.kr/handle/201004/151989 Receptor-mediated endocytosis plays a crucial role in the success of numerous therapies and remains central to advancing drug development. This process begins with ligand binding to specific receptors, triggering the internalization and intracellular trafficking of receptor-ligand complexes. These complexes are subsequently directed into distinct routes, either toward lysosomal degradation or recycling to the cell surface, with implications for therapeutic outcomes. This review examines receptor-ligand interactions as key modulators of endocytosis, emphasizing their role in shaping therapeutic design and efficacy. Advances in selecting receptorligand pairs and engineering ligands with optimized properties have enabled precise control over internalization, endosomal sorting, and trafficking, providing tailored solutions for diverse therapeutic applications. Leveraging these insights, strategies such as RNA-based therapies, antibody-drug conjugates (ADCs), and targeted protein degradation (TPD) platforms have been refined to selectively avoid or promote lysosomal degradation, thereby enhancing therapeutic efficacy. By bridging fundamental mechanisms of receptor-mediated endocytosis with innovative therapeutic approaches, this review offers a framework for advancing precision medicine. English Elsevier BV Receptor-ligand interactions for optimized endocytosis in targeted therapies Article 10.1016/j.jconrel.2025.01.060 1 Journal of Controlled Release, v.380, pp.524 - 538 Journal of Controlled Release 380 524 538 Y scie scopus 001426801800001 2-s2.0-85217414983 Chemistry, Multidisciplinary Pharmacology & Pharmacy Chemistry Pharmacology & Pharmacy Article EPIDERMAL-GROWTH-FACTOR ACQUIRED-RESISTANCE ANTIBODY MIXTURE EGFR LIGANDS CANCER MECHANISMS TRAFFICKING PH AFFINITY DELIVERY Endocytosis Receptor ligand interaction Receptor internalization Antibody drug conjugate Targeted protein degradation