Degraders on Demand: Engineering Smart Nanocarriers for PROTAC Delivery
Antalin Casmie Amalraj1, Vijaya Parthasarathy1
1Department of Nanoscience and Technology, Bharathiar University, Coimbatore, Tamil Nadu 641046, India.
Molecular Pharmaceutics
|December 31, 2025
Summary
Proteolysis-targeting chimeras (PROTACs) offer new therapeutic options but face delivery challenges. Nanocarrier systems enhance PROTACs
Area of Science:
- Drug Delivery and Nanotechnology
- Molecular Biology and Pharmacology
Background:
- Proteolysis-targeting chimeras (PROTACs) are innovative therapeutics for targeted protein degradation.
- Clinical translation of PROTACs is hindered by poor pharmacokinetics, bioavailability, and safety concerns.
Purpose of the Study:
- To review the role of nanocarrier systems in overcoming PROTAC delivery challenges.
- To explore advancements in nanocarrier design for enhanced PROTAC therapy.
- To discuss challenges and future directions for nano-enabled PROTACs.
Main Methods:
- Literature review of PROTAC technology and nanocarrier delivery systems.
- Analysis of physicochemical and biological barriers to PROTACs.
- Summary of recent preclinical applications of nanocarrier-based PROTACs.
- Discussion on AI integration in PROTAC development.
Main Results:
- Nanocarriers improve PROTAC solubility, stability, cellular uptake, and controlled release.
- Nanocarriers enhance tumor accumulation and reduce off-target toxicity of PROTACs.
- Various nanocarrier platforms (liposomes, nanoparticles, exosomes, etc.) show promise.
Conclusions:
- Nanocarrier-based delivery systems are crucial for optimizing PROTAC therapeutic potential.
- Addressing challenges like endosomal escape and tumor heterogeneity is key for clinical success.
- Future research should focus on rational design and overcoming regulatory hurdles for nano-enabled PROTACs.
