Related Experiment Video
Updated: Mar 1, 2026
Genome-Wide CRISPR Screen for Unveiling Radiosensitive and Radioresistant Genes
Published on: May 23, 2025
Local DNA Repair Inhibition for Sustained Radiosensitization of High-Grade Gliomas
Amanda R King1, Christopher D Corso2, Evan M Chen1
1Department of Biomedical Engineering, Yale University, New Haven, Connecticut.
Abstract:
High-grade gliomas, such as glioblastoma (GBM) and diffuse intrinsic pontine glioma (DIPG), are characterized by an aggressive phenotype with nearly universal local disease progression despite multimodal treatment, which typically includes chemotherapy, radiotherapy, and possibly surgery. Radiosensitizers that have improved the effects of radiotherapy for extracranial tumors have been ineffective for the treatment of GBM and DIPG, in part due to poor blood-brain barrier penetration and rapid intracranial clearance of small molecules. Here, we demonstrate that nanoparticles can provide sustained drug release and minimal toxicity. When administered locally, these nanoparticles conferred radiosensitization in vitro and improved survival in rats with intracranial gliomas when delivered concurrently with a 5-day course of fractionated radiotherapy. Compared with previous work using locally delivered radiosensitizers and cranial radiation, our approach, based on the rational selection of agents and a clinically relevant radiation dosing schedule, produces the strongest synergistic effects between chemo- and radiotherapy approaches to the treatment of high-grade gliomas. Mol Cancer Ther; 16(8); 1456-69. ©2017 AACR.
Insights
Nanoparticles effectively deliver radiosensitizers across the blood-brain barrier, improving high-grade glioma treatment. This approach enhances survival in preclinical models by combining chemotherapy and radiotherapy synergistically.
Area of Science:
- Neuro-oncology
- Nanomedicine
- Radiation Oncology
Background:
- High-grade gliomas like glioblastoma (GBM) and diffuse intrinsic pontine glioma (DIPG) are aggressive brain tumors with poor treatment outcomes.
- Conventional radiosensitizers are ineffective for GBM and DIPG due to poor blood-brain barrier (BBB) penetration and rapid clearance.
Purpose of the Study:
- To develop a nanoparticle-based drug delivery system for radiosensitizers to overcome BBB limitations.
- To evaluate the efficacy of nanoparticle-delivered radiosensitizers combined with fractionated radiotherapy for high-grade gliomas.
Main Methods:
- Development of nanoparticles for sustained release of radiosensitizers with minimal toxicity.
- Local administration of nanoparticles concurrently with a 5-day fractionated radiotherapy course in preclinical models.
- Assessment of radiosensitization in vitro and survival improvement in rats with intracranial gliomas.
Main Results:
- Nanoparticles demonstrated sustained drug release and low toxicity.
- Local nanoparticle delivery achieved in vitro radiosensitization.
- Concurrent administration of nanoparticles and radiotherapy significantly improved survival in rats with intracranial gliomas.
Conclusions:
- Nanoparticle-based delivery of radiosensitizers represents a promising strategy for overcoming BBB challenges in treating high-grade gliomas.
- This approach achieved significant synergistic effects between chemotherapy and radiotherapy, offering a potent treatment modality for GBM and DIPG.
- The study highlights the potential of rationally selected agents and clinically relevant radiation schedules for enhanced glioma therapy.
Related Concept Videos
02:57Targeted Cancer Therapies
There are several types of targeted therapies against...
02:36DNA Damage can Stall the Cell Cycle