title: Magnetic core-shell nanocapsules with dual-targeting capabilities and co-delivery of multiple drugs to treat brain gliomas.
abstract: Lactoferrin (Lf)-tethered magnetic double emulsion nanocapsules (Lf-MDCs) are assembled from polyvinyl alcohol (PVA), polyacrylic acid (PAA), and iron oxide (IO) nanoparticles. The core-shell nanostructure of the Lf-MDCs (particle diameters from 100 to 150 nm) can simultaneously accommodate a hydrophilic drug, doxorubicin (Dox), and a hydrophobic drug, curcumin (Cur), in the core and shell, respectively, of the nanocapsules for an efficient drug delivery system. The release patterns of the two drugs can be regulated by manipulating the surface charges and drug-loading ratios, providing the capability for a stepwise adjuvant release to treat cancer cells. The results demonstrate that the dual (Dox+Cur)-drug-loaded nanocapsule can be effectively delivered into RG2 glioma cells to enhance the cytotoxicity against the cells through a synergistic effect. The combined targeting, i.e., magnetic guidance and incorporation of Lf ligands, of these Lf-MDCs results in significantly elevated cellular uptake in the RG2 cells that overexpress the Lf receptor. Interestingly, an intravenous injection of the co-delivered chemotherapeutics follows by magnetic targeting in brain tumor-bearing mice not only achieve high accumulation at the targeted site but also more efficiently suppress cancer growth in vivo than does the delivery of either drug alone.
authors.affiliation: Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu, 300, Taiwan.
authors.forename: Jen-Hung
authors.initials: JH
authors.lastname: Fang
authors.forename: Yen-Ho
authors.initials: YH
authors.lastname: Lai
authors.forename: Tsung-Lang
authors.initials: TL
authors.lastname: Chiu
authors.forename: You-Yin
authors.initials: YY
authors.lastname: Chen
authors.forename: Shang-Hsiu
authors.initials: SH
authors.lastname: Hu
authors.forename: San-Yuan
authors.initials: SY
authors.lastname: Chen
mesh_terms: D000180:Acrylic Resins / Q000737:chemistry; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000633:toxicity; D001932:Brain Neoplasms / Q000188:drug therapy*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003474:Curcumin / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity; D004317:Doxorubicin / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity; D004359:Drug Therapy, Combination; D004655:Emulsions; D005260:Female; D005910:Glioma / Q000188:drug therapy*; D006801:Humans; D008280:Magnetics; D058185:Magnetite Nanoparticles / Q000737:chemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D053769:Nanocapsules / Q000737:chemistry*; D010316:Particle Size
chemical_list: D000180:Acrylic Resins; D000970:Antineoplastic Agents; D004655:Emulsions; D058185:Magnetite Nanoparticles; D053769:Nanocapsules; C006903:carbopol 940; D004317:Doxorubicin; D003474:Curcumin
keywords: brain tumors; double emulsion; multiple drugs; nanocarriers; targeting