title: Self-protecting core-shell magnetic nanoparticles for targeted, traceable, long half-life delivery of BCNU to gliomas.
abstract: The successful delivery of anti-cancer drugs relies on the simultaneous capability to actively target a specific location, a sufficient lifetime in the active form in the circulation, and traceability and quantification of drug distribution via in vivo medical imaging. Herein, a highly magnetic nanocarrier (HMNC) composed of an Fe(3)O(4) core and an aqueous-stable, self-doped poly[N-(1-one-butyric acid)]aniline (SPAnH) shell was chemically synthesized. This nanocarrier exhibited a high capacity for 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) drug loading. BCNU and o-(2-aminoethyl)polyethylene glycol (EPEG) were covalently immobilized on the surface of the HMNC to form a self-protecting magnetic nanomedicine (i.e., SPMNM) that could simultaneously provide low reticuloendothelial system uptake, high active-targeting, and in vivo magnetic resonance imaging (MRI) traceability. Meanwhile, the SPMNM was found to reduce the phagocytosis by macrophages and reduce the hydrolysis rate of BCNU. The high magnetization (approximately 1.2-fold higher than Resovist) of the HMNC allowed efficient magnetic targeting to the tumor. The synergetic drug delivery approach provided approximately a 3.4-fold improvement of the drug's half-life (from 18 h to 62 h) and significantly prolonged the median survival rate in animals that received a low dose of BCNU, compared with those that received a high dose of free BCNU (63 days for those that received 4.5 mg BCNU/kg carried by the nanocarrier versus 50 days for those that received 13.5 mg of free-BCNU). This improvement could enhance the potential of magnetic targeting therapy in clinical applications of cancer treatments.
authors.affiliation: Molecular Medicine Research Center, Department of Chemical and Materials Engineering, Chang Gung University, 259 Wen-Hwa 1st Road, Kuei-Shan, Tao-Yuan 33302, Taiwan, ROC.
authors.forename: Hung-Wei
authors.initials: HW
authors.lastname: Yang
authors.forename: Mu-Yi
authors.initials: MY
authors.lastname: Hua
authors.forename: Hao-Li
authors.initials: HL
authors.lastname: Liu
authors.forename: Chiung-Yin
authors.initials: CY
authors.lastname: Huang
authors.forename: Rung-Ywan
authors.initials: RY
authors.lastname: Tsai
authors.forename: Yu-Jen
authors.initials: YJ
authors.lastname: Lu
authors.forename: Ju-Yu
authors.initials: JY
authors.lastname: Chen
authors.forename: Hsiang-Jun
authors.initials: HJ
authors.lastname: Tang
authors.forename: Han-Yi
authors.initials: HY
authors.lastname: Hsien
authors.forename: Yu-Sun
authors.initials: YS
authors.lastname: Chang
authors.forename: Tzu-Chen
authors.initials: TC
authors.lastname: Yen
authors.forename: Pin-Yuan
authors.initials: PY
authors.lastname: Chen
authors.forename: Kuo-Chen
authors.initials: KC
authors.lastname: Wei
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D002330:Carmustine / Q000494:pharmacology / Q000627:therapeutic use*; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D003198:Computer Simulation; D003432:Cross-Linking Reagents / Q000494:pharmacology; D004247:DNA / Q000378:metabolism; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods*; D004355:Drug Stability; D005910:Glioma / Q000188:drug therapy*; D006207:Half-Life; D006801:Humans; D058185:Magnetite Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D051379:Mice; D057054:Molecular Imaging; D012157:Mononuclear Phagocyte System / Q000187:drug effects; D013696:Temperature; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D003432:Cross-Linking Reagents; D004337:Drug Carriers; D058185:Magnetite Nanoparticles; D004247:DNA; D002330:Carmustine