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Crossing the barrier: treatment of brain tumors using nanochain particles
Efstathios Karathanasis1, Ketan B Ghaghada2
1Department of Biomedical Engineering and Department of Radiology, Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH, USA.
Abstract:
Despite advancements in surgery and radiotherapy, the aggressive forms of brain tumors, such as gliomas, are still uniformly lethal with current therapies offering only palliation complicated by significant toxicities. Gliomas are characteristically diffuse with infiltrating edges, resistant to drugs and nearly inaccessible to systemic therapies due to the brain-tumor barrier. Currently, aggressive efforts are underway to further understand brain-tumor's microenvironment and identify brain tumor cell-specific regulators amenable to pharmacologic interventions. While new potent agents are continuously becoming available, efficient drug delivery to brain tumors remains a limiting factor. To tackle the drug delivery issues, a multicomponent chain-like nanoparticle has been developed. These nanochains are comprised of iron oxide nanospheres and a drug-loaded liposome chemically linked into a 100-nm linear, chain-like assembly with high precision. The nanochain possesses a unique ability to scavenge the tumor endothelium. By utilizing effective vascular targeting, the nanochains achieve rapid deposition on the vascular bed of glioma sites establishing well-distributed drug reservoirs on the endothelium of brain tumors. After reaching the target sites, an on-command, external low-power radiofrequency field can remotely trigger rapid drug release, due to mechanical disruption of the liposome, facilitating widespread and effective drug delivery into regions harboring brain tumor cells. Integration of the nanochain delivery system with the appropriate combination of complementary drugs has the potential to unfold the field and allow significant expansion of therapies for the disease where success is currently very limited. WIREs Nanomed Nanobiotechnol 2016, 8:678-695. doi: 10.1002/wnan.1387 For further resources related to this article, please visit the WIREs website.
Insights
A novel nanochain delivery system effectively targets brain tumors, enabling precise drug release via radiofrequency fields. This breakthrough offers improved glioma treatment by overcoming drug delivery challenges.
Area of Science:
- Nanomedicine
- Biotechnology
- Oncology
Background:
- Aggressive gliomas remain lethal despite current treatments, with drug resistance and the brain-tumor barrier hindering therapy.
- Efficient drug delivery to brain tumors is a critical challenge limiting treatment efficacy.
- Understanding the brain tumor microenvironment is key to developing targeted pharmacologic interventions.
Purpose of the Study:
- To develop a novel nanoparticle system for enhanced drug delivery to gliomas.
- To overcome the limitations of systemic drug delivery across the brain-tumor barrier.
- To enable targeted and remotely triggered drug release within brain tumors.
Main Methods:
- Development of a multicomponent, chain-like nanoparticle (nanochain) composed of iron oxide nanospheres and drug-loaded liposomes.
- Utilizing the nanochain's vascular targeting ability for deposition on glioma tumor endothelium.
- Employing an external low-power radiofrequency field to trigger on-demand drug release through liposome disruption.
Main Results:
- Nanochains demonstrated effective vascular targeting and deposition at glioma sites.
- Remote radiofrequency triggering enabled rapid and widespread drug release into tumor regions.
- The system facilitates efficient drug delivery, overcoming previous limitations.
Conclusions:
- The developed nanochain system shows significant potential for improving glioma therapy.
- Targeted delivery and triggered release address critical challenges in brain tumor treatment.
- Integration with combination therapies could expand treatment options for aggressive brain tumors.
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