Browsing by Author "Chiang, Min-Yu"

Now showing 1 - 10 of 10

Amifostine-conjugated pH-sensitive calcium phosphate-covered magnetic-amphiphilic gelatin nanoparticles for controlled intracellular dual drug release for dual-targeting in HER-2-overexpressing breast cancer
(2015-12-28)
Li, Wei-Ming
;
Chiang, Chih-Sheng
;
Huang, Wei-Chen
;
Su, Chia-Wei
;
Chiang, Min-Yu
We developed a surfactant-free method utilizing amifostine to stably link a targeting ligand (Herceptin) to amphiphilic gelatin (AG)-iron oxide@calcium phosphate (CaP) nanoparticles with hydrophobic curcumin (CUR) and hydrophilic doxorubicin (DOX) encapsulated in the AG core and CaP shell (AGIO@CaP-CD), respectively. This multi-functional nanoparticle system has a pH-sensitive CaP shell and degradable amphiphilic gelatin (AG) core, which enables controllable sequential release of the two drugs. The dual-targeting system of AGIO@CaP-CD (HER-AGIO@CaP-CD) with a bioligand and magnetic targeting resulted in significantly elevated cellular uptake in HER2-overexpressing SKBr3 cells and more efficacious therapy than delivery of targeting ligand alone due to the synergistic cell multi-drug resistance/apoptosis-inducing effect of the CUR and DOX combination. This nanoparticle combined with Herceptin and iron oxide nanoparticles not only provided a dual-targeting functionality, but also encapsulated CUR and DOX as a dual-drug delivery system for the combination therapy. This study further demonstrated that the therapeutic efficacy of this dual-targeting co-delivery system can be improved by modifying the application duration of magnetic targeting, which makes this combination therapy system a powerful new tool for in vitro/in vivo cancer therapy, especially for HER2-positive cancers. (C) 2015 Elsevier B.V. All rights reserved.
Cartilage Tissue-Mimetic Pellets with Multifunctional Magnetic Hyaluronic Acid-Graft-Amphiphilic Gelatin Microcapsules for Chondrogenic Stimulation
(2020-04-01)
Hou, Kai-Ting
;
Liu, Ting-Yu
;
Chiang, Min-Yu
;
Chen, Chun-Yu
;
Chang, Shwu-Jen
Articular cartilage defect is a common disorder caused by sustained mechanical stress. Owing to its nature of avascular, cartilage had less reconstruction ability so there is always a need for other repair strategies. In this study, we proposed tissue-mimetic pellets composed of chondrocytes and hyaluronic acid-graft-amphiphilic gelatin microcapsules (HA-AGMCs) to serve as biomimetic chondrocyte extracellular matrix (ECM) environments. The multifunctional HA-AGMC with specific targeting on CD44 receptors provides excellent structural stability and demonstrates high cell viability even in the center of pellets after 14 days culture. Furthermore, with superparamagnetic iron oxide nanoparticles (SPIOs) in the microcapsule shell of HA-AGMCs, it not only showed sound cell guiding ability but also induced two physical stimulations of static magnetic field(S) and magnet-derived shear stress (MF) on chondrogenic regeneration. Cartilage tissue-specific gene expressions of Col II and SOX9 were upregulated in the present of HA-AGMC in the early stage, and HA-AGMC+MF+S held the highest chondrogenic commitments throughout the study. Additionally, cartilage tissue-mimetic pellets with magnetic stimulation can stimulate chondrogenesis and sGAG synthesis.
Constructing 3D heterogeneous hydrogels from electrically manipulated prepolymer droplets and crosslinked microgels
(2016-10-01)
Chiang, Min-Yu
;
Hsu, Yao-Wen
;
Hsieh, Hsin-Yi
;
Chen, San-Yuan
;
Fan, Shih-Kang
Formation of multifunctional, heterogeneous, and encoded hydrogel building blocks, or microgels, by cross-linking and assembly of microgels are two essential steps in establishing hierarchical, complicated, and three-dimensional (3D) hydrogel architectures that recapitulate natural and biological structures or originate new materials by design. However, for the variety of the hydrogel materials crosslinked differently and for the varied scales of microgels and architectures, the formation and assembly processes are usually performed separately, which increases the manufacturing complexity of designed hydrogel materials. We show the construction of hydrogel architectures through programmable formation and assembly on an electromicrofluidic platform, adopting two reciprocal electric manipulations (electrowetting and dielectrophoresis) to manipulate varied objects (i) in multiple phases, including prepolymer liquid droplets and crosslinked microgels, (ii) on a wide range of scales from micrometer functional particles or cells to millimeter-assembled hydrogel architectures, and (iii) with diverse properties, such as conductive and dielectric droplets that are photocrosslinkable, chemically crosslinkable, or thermally crosslinkable. Prepolymer droplets, particles, and dissolved molecules are electrically addressable to adjust the properties of the microgel building blocks in liquid phase that subsequently undergo crosslinking and assembly in a flexible sequence to accomplish heterogeneous and seamless hydrogel architectures. We expect the electromicrofluidic platform to become a general technique to obtain 3D complex architectures.
Direct Reprogramming of Human Suspension Cells into Mesodermal Cell Lineages via Combined Magnetic Targeting and Photothermal Stimulation by Magnetic Graphene Oxide Complexes
(2017-08-25)
Chiang, Min-Yu
;
Lin, Yi-Zhen
;
Chang, Shwu-Jen
;
Shyu, Woei-Cherng
;
Lu, Huai-En
Suspension cells can provide a source of cells for cellular reprogramming, but they are difficult to transfect by nonviral vectors. An efficient and safe nonviral vector (GO-Fe3O4-PEI complexes) based on iron oxide nanoparticle (Fe3O4)-decorated graphene oxide (GO) complexed with polyethylenimine (PEI) for the first time is developed for delivering three individual episomal plasmids (pCXLE-hOCT3/4-shp53, pCXLE-hSK, and pCXLE-hUL) encoding pluripotent-related factors of Oct3/4, shRNA against p53, Sox2, Klf4, L-Myc, and Lin28 into human peripheral blood mononuclear cells (PBMCs) simultaneously. The combined treatment of magnetic stirring and near-infrared (NIR)-laser irradiation, which can promote contact between the complexes and floating cells and increase the cell membrane permeability, respectively, is used to conduct multiple physical stimulations for suspension PBMCs transfection. The PCR analysis shows that the combinatorial effect of magnetic targeting and photothermal stimulation obviously promoted the transfection efficiency of suspension cells. The transfected cells show positive expression of the pluripotency markers, including Nanog, Oct4, and Sox2, and have potential to differentiate into mesoderm and ectoderm cells. The results demonstrate that the GO-Fe3O4-PEI complex provides a safe, convenient, and efficient tool for reprogramming PBMCs into partially induced pluripotent stem cells, which are able to rapidly transdifferentiate into mesodermal lineages without full reprogramming.
Elastin-like Polypeptide-based Hydrogel Actuator for Cardiac Tissue Engineering
(2017-01-01)
Lo, Yu-Chih
;
Chiang, Min-Yu
;
Chen, Wen-Liang
;
Chen, San-Yuan
;
材料科學與工程學系
Cardiac tissue engineering aims to reconstruct functional construction with resembling native tissue to replace damaged myocardium. To mimic native myocardium, cells with phenotypes of mature cardiomyocytes and scaffolds with elastic, electro-conductive, highly porous, and biodegradable plays two major roles. So far, although a number of cell types have been evaluated in the reports of cardiac repair, most of them cannot form functional cardiomyocytes with mature cardiac phenotypes including the formation of the myocytic syncytium with surrounding cardiomyocytes, and expression of cardiac specific proteins in completely organized pattern. The maturation of cardiomyocytes can be achieved by multiple stimuli such as electrical stimulation, mechanical stretching, and chemical stimulation. Therefore, in this study, we aimed to develop a conductive hydrogel actuator based on elastin-like polypeptide (ELP) consisting of repeating elastin-derived sequences Val-Pro-Gly-Ile-Gly (VPGIG), combining near-infrared light (NIR)-induced mechanical stretching and electrical stimulation for the simulation of immature cardiomyocytes. The hydrogel actuator can be fabricated by rapidly crosslinking by tetrakis(hydroxymethyl) phosphonium chloride (THPC) to form a high density porous structure, providing cardiac muscle cell an extracellular matrix (ECM)-like nanostructure with bioactive Arg-Gly-Asp (RGD) peptide. It showed appropriate mechanical strength and sufficient electroactivity, which is suitable for myocardial cell culture system. In addition, the actuation leads a specific and efficient way to regulate activity in cardiac muscle cell by physical cue of the hydrogel. In the future, we expect the ELP-baesd hydrogel actuator to show great potential to be used in the differentiation and maturation of cardiomyocytes.
ENCODING AND MANIPULATING MICROCOMPONENT ON ELECTROMICROFLUIDIC PLATFORM
(2015)
Chiang, Min-Yu
;
Chen, San-Yuan
;
Fan, Shih-Kang
;
材料科學與工程學系
;
Department of Materials Science and Engineering
We report an electromicrofluidic (EMF) platform for (1) encoding programmable microcomponents (building blocks) using the embedded colloidal particles or mammalian cells and (2) manipulating and assembling microcomponents in two or three dimensions (2D or 3D). This platform is not only accessible to encapsulated particles with various properties, e.g., conductive/dielectric or synthetic/biological, but also to multiple hydrogel materials synthesized differently for further assembly of 2D or 3D complex constructs.
Gene-Embedded Nanostructural Biotic-Abiotic Optoelectrode Arrays Applied for Synchronous Brain Optogenetics and Neural Signal Recording
(2019-03-27)
Huang, Wei-Chen
;
Chi, Hui-Shang
;
Lee, Yi-Chao
;
Lo, Yu-Chun
;
Liu, Ta-Chung
Optogenetics is a recently established neuromodulation technique in which photostimulation is used to manipulate neurons with high temporal and spatial precision. However, sequential genetic and optical insertion with double brain implantation tends to cause excessive tissue damage. In addition, the incorporation of light-sensitive genes requires the utilization of viral vectors, which remains a safety concern. Here, by combining device fabrication design, nanotechnology, and cell targeting technology, we developed a new gene-embedded optoelectrode array for neural implantation to enable spatiotemporal electroporation (EP) for gene delivery/transfection, photomodulation, and synchronous electrical monitoring of neural signals in the brain via one-time implantation. A biotic-abiotic neural interface (called PG) composed of reduced graphene oxide and conductive polyelectrolyte 3,4-ethylenedioxythiophene-modified amphiphilic chitosan was developed to form a nanostructural hydrogel with assembled nanodomains for encapsulating nonviral gene vectors (called PEI-NT-pDNA) formulated by neurotensin (NT) and polyethylenimine (PEI)-coupled plasmid DNA (pDNA). The PG can maintain high charge storage ability to respond to a minimal current of 125 mu A for controllable gene delivery. The in vitro analysis of PG-PEI-NT-pDNA on the microelectrode array chip showed that the microelectrodes provided electrically inductive electropermeabilization, which permitted gene transfection into localized rat adrenal pheochromocytoma cells with a strong green fluorescent protein expression that was up to 8-fold higher than that in nontreated cells. Furthermore, the in vivo implantation enabled on-demand spatiotemporal gene transfection to neurons with 10-fold enhancement of targeting ability compared with astrocytes. Finally, using the real optogenetic opsin channelrhodopsin-2, the flexible neural probe incorporated with an optical waveguide fiber displayed photoevoked extracellular spikes in the thalamic ventrobasal region after focal EP for only 7 days, which provided a proof of concept for the use of photomodulation to facilitate neural therapies.
Label-Free Separation and Sorting of Human Monocytes and T-cells by Electrowetting and Dielectrophoresis
(2013)
Huang, Cheng-Yeh
;
Chiang, Min-Yu
;
Fan, Shih-Kang
;
Ghaemmaghami, Amir M.
;
Hsu, Wensyang
We report a label-free separation and sorting approach based on electrowetting-on-dielectric (EWOD) and dielectrophoresis (DEP) to manipulate human monocyte (THP-1) and T-cell (Jurkat) lines in droplets without any impact on cell viability. In addition to separating cells, this device provides a platform to study cell-cell interactions and migration before the separation.
Sodium Dodecyl Sulfate-Modified Doxorubicin-Loaded Chitosan-Lipid Nanocarrier with Multi Polysaccharide-Lecithin Nanoarchitecture for Augmented Bioavailability and Stability of Oral Administration In Vitro and In Vivo
(2016-05)
Su, Chia-Wei
;
Chiang, Min-Yu
;
Lin, Yu-Ling
;
Tsai, Nu-Man
;
Chen, Yen-Po
For oral anti-cancer drug delivery, a new chitosan-lipid nanoparticle with sodium dodecyl sulfate modification was designed and synthesized using a double emulsification. TEM examination showed that the DOX-loaded nanoparticles, termed D-PL/TG NPs, exhibited a unique core shell configuration composed of multiple amphiphilic chitosan-lecithin reverse micelles as the core and a triglyceride shell as a physical barrier to improve the encapsulation efficiency and reduce the drug leakage. In addition, the D-PL/TG NPs with sodium dodecyl sulfate modification on the surface have enhanced stability in the GI tract and increased oral bioavailability of doxorubicin. In vitro transport studies performed on Caco-2 monolayers indicated that the D-PL/TG NPs enhanced the permeability of DOX in the Caco-2 monolayers by altering the transport pathway from passive diffusion to transcytosis. The in vivo intestinal absorption assay suggested that the D-PL/TG NPs were preferentially absorbed through the specialized membranous epithelial cells (M cells) of the Peyer\'s patches, resulting in a significant improvement (8-fold) in oral bioavailability compared to that of free DOX. The experimental outcomes in this work demonstrate that the D-PL/TG NPs provide an exciting opportunity for advances in the oral administration of drugs with poor bioavailability that are usually used in treating tough and chronic diseases.
Using the interplay of magnetic guidance and controlled TGF-beta release from protein-based nanocapsules to stimulate chondrogenesis
(2018-01-01)
Chiang, Chih-Sheng
;
Chen, Jian-Yi
;
Chiang, Min-Yu
;
Hou, Kai-Ting
;
Li, Wei-Ming
Introduction: Stimulating the proliferation and differentiation of chondrocytes for the regeneration of articular cartilage is a promising strategy, but it is currently ineffective. Although both physical stimulation and growth factors play important roles in cartilage repair, their interplay remains unclear and requires further investigation. In this study, we aimed to clarify their contribution using a magnetic drug carrier that not only can deliver growth factors but also provide an external stimulation to cells in the two-dimensional environment. Materials and methods: We developed a nanocapsule ( transforming growth factor-beta 1 [TGF-beta 1]lo aded magnetic amphiphilic gelatin nanocapsules [MAGNCs]; TGF-beta 1@MAGNCs) composed of hexanoic-anhydride-grafted gelatin and iron oxide nanoparticles to provide a combination treatment of TGF-beta 1 and magnetically induced physical stimuli. With the expression of Arg-Gly-Asp peptide in the gelatin, the TGF-beta 1@MAGNCs have an inherent affinity for chondrogenic ATDC5 cells. Results: In the absence of TGF-beta 1, ATDC5 cells treated with a magnetic field show significantly upregulated Col2a1 expression. Moreover, TGF-beta 1 slowly released from biodegradable TGF-beta 1@MAGNCs further improves the differentiation with increased expression of Col2a1 and Aggrecan. Conclusion: Our study shows the time-dependent interplay of physical stimuli and growth factors on chondrogenic regeneration, and demonstrates the promising use of TGF-beta 1@MAGNCs for articular cartilage repair.