Novel magnetic/ultrasound focusing system enhances nanoparticle drug delivery for glioma treatment.

Abstract

Malignant glioma is a common and severe primary brain tumor with a high recurrence rate and an extremely high mortality rate within 2 years of diagnosis, even when surgical, radiological, and chemotherapeutic interventions are applied. Intravenously administered drugs have limited use because of their adverse systemic effects and poor blood-brain barrier penetration. Here, we combine 2 methods to increase drug delivery to brain tumors. Focused ultrasound transiently permeabilizes the blood-brain barrier, increasing passive diffusion. Subsequent application of an external magnetic field then actively enhances localization of a chemotherapeutic agent immobilized on a novel magnetic nanoparticle. Combining these techniques significantly improved the delivery of 1,3-bis(2-chloroethyl)-1-nitrosourea to rodent gliomas. Furthermore, the physicochemical properties of the nanoparticles allowed their delivery to be monitored by magnetic resonance imaging (MRI). The resulting suppression of tumor progression without damaging the normal regions of the brain was verified by MRI and histological examination. This noninvasive, reversible technique promises to provide a more effective and tolerable means of tumor treatment, with lower therapeutic doses and concurrent clinical monitoring.

• Authors: Pin-Yuan Chen, Hao-Li Liu, Mu-Yi Hua, Hung-Wei Yang, Chiung-Yin Huang, Po-Chun Chu, Lee-Ang Lyu, I-Chou Tseng, Li-Ying Feng, Hong-Chieh Tsai, Shu-Mei Chen, Yu-Jen Lu, Jiun-Jie Wang, Tzu-Chen Yen, Yunn-Hwa Ma, Tony Wu, Jyh-Ping Chen, Jih-Ing Chuang, Jyh-Wei Shin, Chuen Hsueh, Kuo-Chen Wei
• Journal: Neuro-oncology (Neuro Oncol) Vol. 12 Issue 10 Pg. 1050-60 (Oct 2010) ISSN: 1523-5866 [Electronic] England
• PMID: 20663792 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Carmustine

Topics

• Animals
• Antineoplastic Agents (administration & dosage)
• Blood-Brain Barrier (physiology)
• Brain Neoplasms (drug therapy)
• Carmustine (administration & dosage)
• Drug Delivery Systems (methods)
• Glioma (drug therapy)
• High-Energy Shock Waves (therapeutic use)
• Magnetic Resonance Imaging
• Magnetics (methods)
• Male
• Nanoparticles (administration & dosage)
• Rats
• Rats, Sprague-Dawley