Liu Yang, Liu Runhan, Dong Jiawei, Xia Xue, Yang Haoying, Wei Sijun, Fan Linlin, Fang Mengke, Zou Yan, Zheng Meng, Leong Kam W, Shi Bingyang
Henan-Macquarie University Joint Centre for Biomedical Innovation, School of Life Sciences, Henan University, Kaifeng, China.
Henan Key Laboratory of Brain Targeted Bio-Nanomedicine, School of Life Sciences, Henan University, Kaifeng, China.
Nat Nanotechnol. 2025 Feb;20(2):296-302. doi: 10.1038/s41565-024-01801-3. Epub 2024 Oct 28.
Strategies that selectively bind proteins of interest and target them to the intracellular protein recycling machinery for targeted protein degradation have recently emerged as powerful tools for undruggable targets in biomedical research and the pharmaceutical industry. However, targeting any new protein of interest with current degradation tools requires a laborious case-by-case design for different diseases and cell types, especially for extracellular targets. Here we observe that nanoparticles can mediate specific receptor-independent internalization of a bound protein and further develop a general strategy for degradation of extracellular proteins of interest by making full use of clinically approved components. This extremely flexible strategy aids in targeted protein degradation tool development and provides knowledge for targeted drug therapies and nanomedicine design.
最近，选择性结合感兴趣的蛋白质并将其靶向细胞内蛋白质回收机制以进行靶向蛋白质降解的策略，已成为生物医学研究和制药行业中针对不可成药靶点的强大工具。然而，使用当前的降解工具针对任何新的感兴趣蛋白质，都需要针对不同疾病和细胞类型进行费力的逐个案例设计，尤其是针对细胞外靶点。在这里，我们观察到纳米颗粒可以介导结合蛋白的特异性非受体介导内化，并通过充分利用临床批准的成分，进一步开发出一种降解感兴趣的细胞外蛋白质的通用策略。这种极其灵活的策略有助于靶向蛋白质降解工具的开发，并为靶向药物治疗和纳米医学设计提供知识。
