Browsing by Author "Chiu, Tsung-Lang"

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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
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Chiu, Tsung-Lang
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Huang, Wei-Chen
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Lai, Yen-Ho
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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
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Lai, Yen-Ho
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Chiu, Tsung-Lang
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Chen, You-Yin
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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.
SPIO nanoparticle-stabilized PAA-F127 thermosensitive nanobubbles with MR/US dual-modality imaging and HIFU-triggered drug release for magnetically guided in vivo tumor therapy
(2013-11-28)
Huang, Hsin-Yang
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Hu, Shang-Hsiu
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Hung, Shih-Ya
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Chiang, Chih-Sheng
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Liu, Hao-Li
Nanobubbles can serve as promising, next-generation theranostic platforms for ultrasound (US) and magnetic resonance (MR) imaging, and combined magnetic targeting (MT) and high-intensity focused ultrasound (HIFU)-triggered drug release for tumor therapy. Nanobubble-based dual contrast enhancement agents encapsulated with perfluoropentane and stabilized with superparamagnetic iron oxide (SPIO) nanoparticles have been synthesized through a single-step emulsion process from thermosensitive F127 and polyacrylic acid (PAA). Both US and MR imaging contrast can be optimized by varying the shell thickness and SPIO-embedded concentration. The US contrast can be enhanced from a mean gray value of 62 to 115, and the MR r(2) value can be enhanced from 164 to 208 (s(-1) mM(-1) Fe) by increasing the SPIO concentration from 14.1 to 28.2 mg/mL, respectively. In vivo investigations of SPIO-embedded nanobubbles in excised tumors under external MT revealed that the US and MR signals change quantitatively compared to the same site without MT. This combined strategy enables the nanobubbles to enhance both passive targeting (increasing the permeability by HIFU) and physical MT of chemotherapeutic drugs to tumors. The integration of functionalities makes this nanobubble system a powerful and viable new tool to achieve simultaneous in vivo tumor imaging and efficacious cancer therapy. (C) 2013 Published by Elsevier B.V.
Surfactant-Free, Lipo-Polymersomes Stabilized by Iron Oxide Nanoparticles/Polymer Interlayer for Synergistically Targeted and Magnetically Guided Gene Delivery
(2014-02-01)
Hu, Shang-Hsiu
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Hsieh, Tsung-Ying
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Chiang, Chin-Sheng
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Chen, Po-Jung
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Chen, You-Yin
Gene therapy holds promise to suppress carcinomas but still remains far removed from clinic because of the lack of a safe and effective delivery system. Besides enhancing transfection efficiency, the difficulty in gene therapy is how to deliver sufficient gene molecules to the site of interest. Herein, the rational design of surfactant-free lipo-polymersomes (LPPs) to overcome these problems is reported, simultaneously using a lipid-stabilized double emulsion approach. The LPPs are designed to conceal the cationic lipids and plasmid DNA inside the core along with iron oxide nanoparticles/polymer interlayer and a relatively neutral lipid shell to avoid the undesired interaction during circulation, leading to high accumulation in the tumors of mice. Furthermore, guided by an external magnetic field and the folic acid (FA) that target tumors via folate receptor-mediated endocytosis on the cell surface, the vectors demonstrate a 30-40-fold increase in cell uptake. Moreover, this synergistic tumor-targeted approach can enhance a 10-fold increase in in vivo transfection efficacy by promoting the delivery of LPPs to cancer cells and facilitating the endosomal escape of gene molecules. The new insights and capabilities represent a major step in nanovector engineering for safe and efficient gene delivery.