Browsing by Author "Lai, Yen-Ho"

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Combination of fucoidan-based magnetic nanoparticles and immunomodulators enhances tumour-localized immunotherapy
(2018-08-01)
Chiang, Chih-Sheng
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Lin, Yu-Jung
;
Lee, Rachel
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Lai, Yen-Ho
;
Cheng, Hung-Wei
Checkpoint immunotherapy that inhibits tumour immune evasion has demonstrated significant clinical success. However, the therapeutic response is limited to certain patient populations, and immunotoxicity as well as autoimmunity have compromised the therapeutic benefits. Here, we report on an inherently therapeutic fucoidan-dextran-based magnetic nanomedicine (IO@FuDex(3)) conjugated with a checkpoint inhibitor (anti-PD-L1) and T-cell activators (anti-CD3 and anti-CD28). IO@FuDex(3 )can repair the immunosuppressive tumour microenvironment by reinvigorating tumour-infiltrating lymphocytes, while targeting the nanomedicine via magnetic navigation to the tumour to minimize off-target effects. Treatment that combines IO@FuDex(3) and magnetic navigation reduces the occurrence of adverse events and extends the median survival from 32 to 63 days with less than 1per cent dose compared with soluble anti-PD-L1. Thus, we demonstrate the potential of integrating anti-PD-L1 and T-cell activators as a form of inherently therapeutic nanomedicine to augment the therapeutic index of combination checkpoint immunotherapy.
Development and Characterization of a Fucoidan-Based Drug Delivery System by Using Hydrophilic Anticancer Polysaccharides to Simultaneously Deliver Hydrophobic Anticancer Drugs
(2020-07-01)
Lai, Yen-Ho
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Chiang, Chih-Sheng
;
Hsu, Chin-Hao
;
Cheng, Hung-Wei
;
Chen, San-Yuan
Fucoidan, a natural sulfated polysaccharide, which can activate the immune response and lessen adverse effects, is expected to be an adjuvant agent in combination with chemotherapy. Using natural hydrophilic anticancer polysaccharides to simultaneously encapsulate hydrophobic anticancer drugs is feasible, and a reduced side effect can be achieved to amplify the therapeutic efficacy. In this study, a novel type of fucoidan-PLGA nanocarrier (FPN-DTX) was developed for the encapsulation of the hydrophobic anticancer drug, docetaxel (DTX), as a drug delivery system. From the comparison between FPN-DTX and the PLGA particles without fucoidan (PLGA-DTX), FPNs-DTX with fucoidan were highly stable with smaller sizes and dispersed well without aggregations in an aqueous environment. The drug loading and release can be further modified by modulating relative ratios of Fucoidan (Fu) to PLGA. The (FPN 3-DTX) nanoparticles with a 10:3 ratio of Fu:PLGA displayed uniform particle size with higher encapsulation efficiency than PLGA NPs and sustained drug release ability. The biocompatible fucoidan-PLGA nanoparticles displayed low cytotoxicity without drug loading after incubation with MDA-MB-231 triple-negative breast cancer cells. Despite lower cellular uptake than that of PLGA-DTX due to a higher degree of negative zeta potential and hydrophilicity, FPN 3-DTX effectively exerted better anticancer ability, so FPN 3-DTX can serve as a competent drug delivery system.
Dual-drug nanomedicine with hydrophilic F127-modified magnetic nanocarriers assembled in amphiphilic gelatin for enhanced penetration and drug delivery in deep tumor tissue
(2018-01-01)
Lai, Yen-Ho
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Chiang, Chih-Sheng
;
Kao, Tzu-Hsun
;
Chen, San-Yuan
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材料科學與工程學系
Introduction: Deep penetration of large-sized drug nanocarriers into tumors is important to improve the efficacy of tumor therapy. Methods: In this study, we developed a size-changeable "Trojan Horse" nanocarrier (THNC) composed of paclitaxel (PTX)-loaded Greek soldiers (GSs; similar to 20 nm) assembled in an amphiphilic gelatin matrix with hydrophilic losartan (LST) added. Results: With amphiphilic gelatin matrix cleavage by matrix metalloproteinase-2, LST showed fast release of up to 60% accumulated drug at 6 h, but a slow release kinetic (similar to 20%) was detected in the PTX from the GSs, indicating that THNCs enable controllable release of LST and PTX drugs for penetration into the tumor tissue. The in vitro cell viability in a 3D tumor spheroid model indicated that the PTX-loaded GSs liberated from THNCs showed deeper penetration as well as higher cytotoxicity, reducing a tumor spheroid to half its original size and collapsing the structure of the tumor microenvironment. Conclusion: The results demonstrate that the THNCs with controlled drug release and deep penetration of magnetic GSs show great potential for cancer therapy.
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
;
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.
Morphological and structural evolution of mesoporous calcium aluminate nanocomposites by microwave-assisted synthesis
(2014-01-01)
Chang, Yen-Po
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Chang, Po-Hsueh
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Lee, Yuan-Tse
;
Lee, Tai-Jung
;
Lai, Yen-Ho
Novel special dual-structure calcium aluminate nanocomposites consisting of mesoporous Ca-containing Al2O3 nanonetworks with Ca12Al14O33 polycrystalline nanorods have been successfully synthesized using the microwave-hydrothermal (M-H) process in an alcohol solution consisting of calcium nitrate and mesoporous alumina, followed by calcination at a lower temperature (e.g., less than 600 degrees C). The mesoporous Ca-containing aluminate nanocomposites possessed a specific surface area of 51 m(2) g(-1) and a broad pore size distribution of 4-12 nm in diameter, as observed from N-2 adsorption/desorption measurements. The results showed that highly dispersed Ca12Al14O33 nanorods grown on the mesoporous nanostructure were obtained by varying the molar ratio of Ca/Al or by controlling microwave heating time, as characterized by scanning electron microscopy (SEM), transmission electron microscopy/electronic energy loss spectroscopy (TEM/EELS) and powder X-ray diffraction (PXRD). The Ca12Al14O33 nanorods with diameters of 50-100 nm and lengths of 200-400 nm were grown in and on the one-dimensional mesochannels. A formation mechanism of the mesoporous Ca-containing aluminate nanocomposites involving amorphous mesoporous hydrated-Al2O3 was also proposed. (C) 2013 Elsevier Inc. All rights reserved.
Synthesis, characterization and high temperature CO2 capture capacity of nanoscale Ca-based layered double hydroxides via reverse microemulsion
(2014-02-15)
Chang, Po-Hsueh
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Chang, Yen-Po
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Lai, Yen-Ho
;
Chen, San-Yuan
;
Yu, Ching-Tsung
In this study, we report a reverse microemulsion method to prepare stable homogeneous suspensions containing dispersed Ca-Al layered double hydroxide (LDH) nanoparticles. By changing the concentration, reaction time and temperature, the nano-particles with different structural morphology was developed from amorphous aggregation to platelet, regular hexagon and hydrangea-like hierarchical structure. The crystallization and growth of Ca-Al LDH nanoparticles were involved with a nucleation and growth process under nonaqueous polar solvent/surfactant system. After calcination at 700 degrees C, the calcined nano-sized Cal-Al LDH powders synthesized from the reverse microemulsion display remarkable CO2 capture behavior at 600 degrees C, which is strongly dependent on the reaction conditions (concentration, time and temperature). The calcined powder synthesized at 80 degrees C exhibits a faster rate of CO2 absorption and higher CO2 capture capacity of 44 wt% CO2 without apparent degradation under multiple cycles of carbonation-calcination. (C) 2013 Elsevier B. V. All rights reserved.