title: 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.affiliation: Department of Neurosurgery, Chang-Gung University and Memorial Hospital, Taoyuan 333.
authors.forename: Pin-Yuan
authors.initials: PY
authors.lastname: Chen
authors.forename: Hao-Li
authors.initials: HL
authors.lastname: Liu
authors.forename: Mu-Yi
authors.initials: MY
authors.lastname: Hua
authors.forename: Hung-Wei
authors.initials: HW
authors.lastname: Yang
authors.forename: Chiung-Yin
authors.initials: CY
authors.lastname: Huang
authors.forename: Po-Chun
authors.initials: PC
authors.lastname: Chu
authors.forename: Lee-Ang
authors.initials: LA
authors.lastname: Lyu
authors.forename: I-Chou
authors.initials: IC
authors.lastname: Tseng
authors.forename: Li-Ying
authors.initials: LY
authors.lastname: Feng
authors.forename: Hong-Chieh
authors.initials: HC
authors.lastname: Tsai
authors.forename: Shu-Mei
authors.initials: SM
authors.lastname: Chen
authors.forename: Yu-Jen
authors.initials: YJ
authors.lastname: Lu
authors.forename: Jiun-Jie
authors.initials: JJ
authors.lastname: Wang
authors.forename: Tzu-Chen
authors.initials: TC
authors.lastname: Yen
authors.forename: Yunn-Hwa
authors.initials: YH
authors.lastname: Ma
authors.forename: Tony
authors.initials: T
authors.lastname: Wu
authors.forename: Jyh-Ping
authors.initials: JP
authors.lastname: Chen
authors.forename: Jih-Ing
authors.initials: JI
authors.lastname: Chuang
authors.forename: Jyh-Wei
authors.initials: JW
authors.lastname: Shin
authors.forename: Chuen
authors.initials: C
authors.lastname: Hsueh
authors.forename: Kuo-Chen
authors.initials: KC
authors.lastname: Wei
mesh_terms: 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
chemical_list: D000970:Antineoplastic Agents; D002330:Carmustine