Browsing by Author "Fang, Jen-Hung"

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Dual-Targeting Lactoferrin-Conjugated Polymerized Magnetic Polydiacetylene-Assembled Nanocarriers with Self-Responsive Fluorescence/Magnetic Resonance Imaging for In Vivo Brain Tumor Therapy
(2016-03-23)
Fang, Jen-Hung
;
Chiu, Tsung-Lang
;
Huang, Wei-Chen
;
Lai, Yen-Ho
;
Hu, Shang-Hsiu
Maintaining a high concentration of therapeutic agents in the brain is diffi cult due to the restrictions of the blood-brain barrier (BBB) and rapid removal from blood circulation. To enable controlled drug release and enhance the blood-brain barrier (BBB)-crossing effi ciency for brain tumor therapy, a new dual-targeting magnetic polydiacetylene nanocarriers (PDNCs) delivery system modifi ed with lactoferrin (Lf) is developed. The PDNCs are synthesized using the ultraviolet (UV) cross-linkable 10,12-pentacosadiynoic acid (PCDA) monomers through spontaneous assembling onto the surface of superparamagnetic iron oxide (SPIO) nanoparticles to form micelles-polymerized structures. The results demonstrate that PDNCs will reduce the drug leakage and further control the drug release, and display self-responsive fl uorescence upon intracellular uptake for cell traffi cking and imaging-guided tumor treatment. The magnetic Lf-modifi ed PDNCs with magnetic resonance imaging (MRI) and dual-targeting ability can enhance the transportation of the PDNCs across the BBB for tracking and targeting gliomas. An enhanced therapeutic effi ciency can be obtained using Lf-Cur (Curcumin)-PDNCs by improving the retention time of the encapsulated Cur and producing fourfold higher Cur amounts in the brain compared to free Cur. Animal studies also confi rm that Lf targeting and controlled release act synergistically to signifi cantly suppress tumors in orthotopic brain-bearing rats.
Magnetic Core-Shell Nanocapsules with Dual-Targeting Capabilities and Co-Delivery of Multiple Drugs to Treat Brain Gliomas
(2014-08-01)
Fang, Jen-Hung
;
Lai, Yen-Ho
;
Chiu, Tsung-Lang
;
Chen, You-Yin
;
Hu, Shang-Hsiu
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.