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Nanoenabled Strategies Enhancing PROTACs for Cancer Therapy
Rui Li1, Shuhao Zhang1, Yunxue Xu1,2
1Department of Biomedical Engineering, College of Future Technology, National Biomedical Imaging Center, State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing 100871, China.
Nanotechnology enhances proteolysis-targeting chimeras (PROTACs) for cancer therapy by improving delivery and enabling new modalities. This approach addresses challenges like poor solubility and bioavailability for better tumor targeting and efficacy.
Area of Science:
- Oncology
- Nanotechnology
- Drug Delivery
Background:
- Proteolysis-targeting chimeras (PROTACs) offer a novel therapeutic strategy for cancer by degrading target proteins.
- Clinical translation of PROTACs is hindered by poor solubility, high molecular weight, and metabolic instability, limiting bioavailability and tumor penetration.
Purpose of the Study:
- To review nanotechnology-enabled strategies for improving PROTAC delivery and therapeutic potential in cancer.
- To highlight challenges and future directions for the clinical advancement of PROTACs.
Main Methods:
- Review of nanocarrier systems for enhancing PROTAC stability, pharmacokinetics, and tumor accumulation.
- Exploration of nanotechnology in developing next-generation PROTACs (e.g., mRNA-encoded, RNA-scaffolded).
- Discussion of stimuli-responsive nanocarriers for controlled PROTAC release.
Main Results:
- Nanocarriers improve PROTAC stability, bioavailability, and tumor-specific delivery.
- Nanotechnology facilitates novel PROTAC modalities with expanded therapeutic applications.
- Stimuli-responsive systems enable spatiotemporal control over PROTAC release, enhancing efficacy and reducing off-target effects.
Conclusions:
- Nanotechnology-based strategies are crucial for overcoming PROTAC delivery challenges in cancer therapy.
- Further development is needed to facilitate the clinical translation of these advanced PROTAC formulations.
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