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Updated: Jul 1, 2025
Polymalic Acid-based Nano Biopolymers for Targeting of Multiple Tumor Markers: An Opportunity for Personalized Medicine?
Published on: June 13, 2014
Radiation responsive PROTAC nanoparticles for tumor-specific proteolysis enhanced radiotherapy
Mengxia Xu1, Yuyang Yun1,2, Changjun Li1
1State Key Laboratory of Natural Medicines, Key Laboratory of Drug Quality Control and Pharmacovigilance, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China. xiaolian_sun@cpu.edu.cn.
This study introduces a novel X-ray radiation-responsive Proteolysis Targeting Chimera (PROTAC) nanomicelle. This innovation enables targeted cancer therapy with reduced toxicity and enhanced radiosensitivity by degrading BRD4 protein upon X-ray exposure.
Area of Science:
- Biomedical Engineering
- Oncology
- Drug Delivery
Background:
- Proteolysis Targeting Chimeras (PROTACs) offer a promising cancer therapy approach.
- However, their continuous activity can cause off-target toxicity, limiting efficacy.
- Developing controlled PROTAC activation is crucial for improving antitumor performance.
Purpose of the Study:
- To engineer an X-ray radiation-responsive PROTAC nanomicelle (RCNprotac) for targeted cancer treatment.
- To overcome the limitations of non-specific toxicity associated with conventional PROTACs.
- To investigate the synergistic effects of RCNprotac and X-ray radiation in cancer therapy.
Main Methods:
- Conjugation of a PROTAC (MZ1) to hydrophilic PEG via a diselenide bond-containing chain to form RCNprotac.
- Self-assembly of RCNprotac into nanomicelles (141.80 ± 5.66 nm).
- Evaluation of RCNprotac's bioactivity, tumor accumulation, and drug release upon X-ray irradiation.
Main Results:
- RCNprotac exhibited no circulation bioactivity until X-ray triggered release of MZ1.
- Nanomicelles effectively accumulated at tumor sites via the enhanced permeability and retention effect.
- X-ray-induced MZ1 release led to BRD4 protein degradation, enhancing tumor radiosensitivity both in vitro and in vivo.
Conclusions:
- X-ray-responsive PROTAC nanomicelles offer a spatiotemporally controlled protein degradation strategy.
- This approach enhances tumor radiosensitivity through BRD4 proteolysis.
- RCNprotac presents a novel platform for targeted cancer therapy with improved safety and efficacy.
