Nano-targeted protein degradation: Ushering in a new era of protein degradation therapeutics

Miaoxizi Luo; Jiaqi Ma; Chuan Hu; Qi Zou; Jingjing Li; Hang Yin; Qian Cheng; Jinming Zhang; Ruibing Wang

doi:10.59717/j.xinn-drugdisc.2026.100005

The Innovation Drug Discovery > 2026 Vol. 1 > No. 1 > 100005

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Nano-targeted protein degradation: Ushering in a new era of protein degradation therapeutics

1.
State Key Laboratory of Mechanism and Quality of Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macau SAR 999078, China
2.
Chinese Medicine Germplasm Resources Innovation and Effective Uses Key Laboratory of Sichuan Province, Chengdu University of Traditional Chinese Medicine, Chengdu 611130, China
3.
Department of Rehabilitation Sciences, Faculty of Health and Social Sciences, Hong Kong Polytechnic University, Hong Kong SAR 999077, China
4.
Research School of Chemistry, Australian National University, Canberra, ACT 2601, Australia
5.
These authors contributed equally

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Corresponding authors: chengqian@cdutcm.edu.cn (Q.C.); cdutcmzjm@126.com (J.Z.); rwang@um.edu.mo (R.W.)
Received Date: January 23, 2026

Accepted Date: March 28, 2026

Published Online: April 13, 2026

The Innovation Drug Discovery 1(1), https://doi.org/10.59717/j.xinn-drugdisc.2026.100005 | Cite this article

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GRAPHICAL ABSTRACT

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PUBLIC SUMMARY

PUBLIC SUMMARY
1. Targeted protein degradation (TPD) has emerged as a transformative therapeutic strategy.
  
  This review provides a comprehensive overview of Nano-TPD.
  
  Nano-TPD is a next-generation therapeutic strategy with broad applicability.

ABSTRACT

ABSTRACT

Targeted protein degradation (TPD) has emerged as a transformative therapeutic strategy that overcomes the limitations of conventional small-molecule inhibitors (SMIs) by harnessing the degradation machinery, including the ubiquitin-proteasome system (UPS) and lysosomal pathway. However, traditional TPD agents face substantial challenges in clinical translation, such as poor solubility, low bioavailability, insufficient targeting specificity, and limited tissue penetration. To address these limitations, the integration of nanotechnology has given rise to Nano-TPD as a new generation therapeutic platform that revolutionizes TPD delivery. We first summarize the recent advances in TPD technology for the treatment of common clinical diseases, highlighting key molecular targets and representative degraders. Then, we focus on the design of Nano-TPD platforms, including lipid-based, polymeric, inorganic, and biomimetic nanocarriers, as well as innovative strategies. The core mechanisms of Nano-TPD, encompassing targeted delivery, intracellular trafficking, stimuli-triggered release, and enhanced protein degradation via UPS or lysosomal pathways, are systematically elaborated. Furthermore, we discuss the challenges and future perspectives of Nano-TPD. This review provides a comprehensive overview of Nano-TPD, emphasizing its role in advancing TPD toward clinical utility and expanding its therapeutic scope across various diseases.
- Targeted protein degradation /
- Nanoparticles /
- Drug delivery /
- PROTACs

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Luo M., Ma J., Hu C., et al. (2026). Nano-targeted protein degradation: Ushering in a new era of protein degradation therapeutics. The Innovation Drug Discovery 1:100005. https://doi.org/10.59717/j.xinn-drugdisc.2026.100005

Luo M., Ma J., Hu C., et al. (2026). Nano-targeted protein degradation: Ushering in a new era of protein degradation therapeutics. The Innovation Drug Discovery 1:100005. https://doi.org/10.59717/j.xinn-drugdisc.2026.100005

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