2. Academic Validation
  3. Targeted protein degradation via cellular trafficking of nanoparticles

Targeted protein degradation via cellular trafficking of nanoparticles

  • Nat Nanotechnol. 2024 Oct 28. doi: 10.1038/s41565-024-01801-3.
Yang Liu # 1 2 3,  Runhan Liu # 1 2,  Jiawei Dong 1 2,  Xue Xia 1 2,  Haoying Yang 2,  Sijun Wei 1 2,  Linlin Fan 2,  Mengke Fang 2,  Yan Zou 1 2 4,  Meng Zheng 5 6 7,  Kam W Leong 8,  Bingyang Shi 9 10 11 12
Affiliations

Affiliations

  • 1 Henan-Macquarie University Joint Centre for Biomedical Innovation, School of Life Sciences, Henan University, Kaifeng, China.
  • 2 Henan Key Laboratory of Brain Targeted Bio-Nanomedicine, School of Life Sciences, Henan University, Kaifeng, China.
  • 3 Huaihe Hospital of Henan University, Henan University, Kaifeng, China.
  • 4 Macquarie Medical School, Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, New South Wales, Australia.
  • 5 Henan-Macquarie University Joint Centre for Biomedical Innovation, School of Life Sciences, Henan University, Kaifeng, China. mzheng@henu.edu.cn.
  • 6 Henan Key Laboratory of Brain Targeted Bio-Nanomedicine, School of Life Sciences, Henan University, Kaifeng, China. mzheng@henu.edu.cn.
  • 7 Huaihe Hospital of Henan University, Henan University, Kaifeng, China. mzheng@henu.edu.cn.
  • 8 Department of Biomedical Engineering, Columbia University, New York, NY, USA. kam.leong@columbia.edu.
  • 9 Henan-Macquarie University Joint Centre for Biomedical Innovation, School of Life Sciences, Henan University, Kaifeng, China. bs@henu.edu.cn.
  • 10 Macquarie Medical School, Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, New South Wales, Australia. bs@henu.edu.cn.
  • 11 Department of Biomedical Engineering, Columbia University, New York, NY, USA. bs@henu.edu.cn.
  • 12 School of Biomedical Engineering, University of Technology Sydney, Sydney, New South Wales, Australia. bs@henu.edu.cn.
  • # Contributed equally.
PMID: 39468359 DOI: 10.1038/s41565-024-01801-3
Abstract

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.

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