Novel magnetic/ultrasound focusing system enhances nanoparticle drug delivery for glioma treatment.
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.
Chen
Pin-Yuan
PY
Department of Neurosurgery, Chang-Gung University and Memorial Hospital, Taoyuan 333.
Liu
Hao-Li
HL
Hua
Mu-Yi
MY
Yang
Hung-Wei
HW
Huang
Chiung-Yin
CY
Chu
Po-Chun
PC
Lyu
Lee-Ang
LA
Tseng
I-Chou
IC
Feng
Li-Ying
LY
Tsai
Hong-Chieh
HC
Chen
Shu-Mei
SM
Lu
Yu-Jen
YJ
Wang
Jiun-Jie
JJ
Yen
Tzu-Chen
TC
Ma
Yunn-Hwa
YH
Wu
Tony
T
Chen
Jyh-Ping
JP
Chuang
Jih-Ing
JI
Shin
Jyh-Wei
JW
Hsueh
Chuen
C
Wei
Kuo-Chen
KC
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D001812:Blood-Brain Barrier / Q000502:physiology; D001932:Brain Neoplasms / Q000188:drug therapy*; D002330:Carmustine / Q000008:administration & dosage; D016503:Drug Delivery Systems / Q000379:methods*; D005910:Glioma / Q000188:drug therapy*; D019220:High-Energy Shock Waves / Q000627:therapeutic use*; D008279:Magnetic Resonance Imaging; D008280:Magnetics / Q000379:methods; D008297:Male; D053758:Nanoparticles / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000970:Antineoplastic Agents; D002330:Carmustine