Related Experiment Video
Updated: Sep 13, 2025
Surface-enhanced Resonance Raman Scattering Nanoprobe Ratiometry for Detecting Microscopic Ovarian Cancer via Folate Receptor Targeting
Published on: March 25, 2019
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.
Abstract:
Proteolysis-targeting chimeras (PROTACs) have emerged as a breakthrough therapeutic strategy in oncology, enabling the selective degradation of traditionally "undruggable" proteins via the ubiquitin-proteasome system. However, their clinical translation remains challenging due to high molecular weight, limited aqueous solubility, and metabolic instability, which limit systemic bioavailability and tumor penetration. To address these challenges, a variety of nanocarrier systems have been developed to improve the stability, pharmacokinetics, and tumor-specific accumulation of PROTACs. Beyond delivery enhancement, nanotechnology also enables the creation of next-generation PROTAC modalities, such as mRNA-encoded and RNA-scaffolded PROTACs, thereby expanding their therapeutic potential. In parallel, stimuli-responsive nanocarriers offer spatiotemporal control over PROTAC release, maximizing therapeutic efficacy while minimizing off-target effects. This review provides a comprehensive overview of nanotechnology-enabled strategies for PROTAC delivery, highlights key translational challenges, and discusses future directions to facilitate their clinical advancement in cancer therapy.
Insights
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.
Related Concept Videos
02:57Targeted Cancer Therapies
There are several types of targeted therapies against...
02:50Combination Therapies and Personalized Medicine
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
02:49Cancer Therapies
However, cancer treatments can pose several challenges, as therapies used to kill cancer cells are generally also toxic to normal cells. Moreover, cancer cells mutate rapidly and can develop resistance to chemical agents or radiation therapy. Besides, all types of cancer cells may not respond to the same therapy. Some cancer cells respond to one...