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Advanced nanotechnologies for protein modulation: From Nano-PROTAC to Nano-APROM.

Jie Wang1, Xi Hu2, Jingxin Zhang3

  • 1National Center for Translational Medicine (Shanghai) Hefei Branch, School of Pharmacy, Anhui Province Key Laboratory of Pharmaceutical Preparation Technology and Application, Anhui Academy of Chinese Medicine, Anhui University of Chinese Medicine, Hefei, Anhui 230038, China; Joint R&D Center for Structural Imaging and Metabolic-Immunoregulatory Technologies in Integrated Traditional Chinese and Modern Medicine, Shanghai Jiao Tong University, Shanghai 200240, China; School of Chemistry and Chemical Engineering, Hefei University of Technology, Hefei, Anhui 230009, China.

Journal of Controlled Release : Official Journal of the Controlled Release Society
|April 5, 2026
PubMed
Summary

Nanoscale engineering advances protein modulation therapies. Nanoscale proteolysis-targeting chimeras (nano-PROTACs) and nanoscale artificial protein modulators (nano-APROMs) offer precise control over protein degradation and function for disease treatment.

Keywords:
Nano-PROTACsNanoscale artificial protein modulators (nano-APROMs)Protein modulationProteolysis-targeting chimeras (PROTACs)

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Area of Science:

  • Biomedical Engineering
  • Nanotechnology
  • Molecular Biology

Background:

  • Protein homeostasis is crucial in disease pathogenesis.
  • Targeted protein modulation is a key therapeutic strategy.
  • Nanoscale architectures enhance delivery and control of protein-targeting agents.

Purpose of the Study:

  • To review advances in nanoscale proteolysis-targeting chimeras (nano-PROTACs) for protein degradation.
  • To discuss nanoscale artificial protein modulators (nano-APROMs) for protein function regulation.
  • To explore design principles, therapeutic applications, and future directions in protein-targeting nanomedicine.

Main Methods:

  • Analysis of nanoscale architectural design principles for nano-PROTACs.
  • Assessment of therapeutic implementation strategies for nano-PROTACs.
  • Discussion of design strategies and applications of nano-APROMs, including nanocarrier-mediated delivery and atomic-level engineering.

Main Results:

  • Rational design of nano-PROTACs improves delivery and fine-tunes ubiquitin-proteasome degradation kinetics.
  • Atomic-level engineering of nano-APROMs enables systematic reprogramming of aberrant protein function.
  • Integrated nano-bio systems offer enhanced efficiency, spatiotemporal control, and expanded regulatory modalities.

Conclusions:

  • Nanoscale approaches represent a transformative frontier in protein-targeting nanomedicine.
  • Further research into structural design, structure-activity relationships, and nano-bio interactions is needed.
  • Addressing challenges and exploring opportunities will drive future clinical development in this field.