Browsing by Author "Hu, Shang-Hsiu"

Now showing 1 - 20 of 44

A flexible drug delivery chip for the magnetically-control led release of anti-epileptic drugs
(2009-11-03)
Huang, Wei-Chen
;
Hu, Shang-Hsiu
;
Liu, Kun-Ho
;
Chen, San-Yuan
;
Liu, Dean-Mo
A flexible drug delivery device was designed and fabricated using electrophoretic deposition of drug-carrying magnetic core-shell Fe(3)O(4) at SiO(2) nanoparticles onto an electrically conductive flexible PET substrate. The PET substrate was first patterned to a desired layout and subjected to deposition. In doing so, a uniform and nanoporous membrane could be produced. After lamination of the patterned membranes, a final chip-like device of thickness less than 0.5 mm is formed that is used for controlled delivery of an anti-epileptic drug, i.e., ethosuximide (ESM). The release of useful drugs can be controlled by directly modulating the magnetic field, and the chip is capable of demonstrating a variety of release profiles (i.e., slow release, sustained release, step-wise release and burst release profiles). These profiles can follow a wide spectrum of patterns ranging from zero to pulsatile release kinetics depending on the mode of magnetic operation. When the magnetic field was removed, the release behavior was instantly ceased, and vice versa. A preliminary in-vivo study using Long-Evans rat model has demonstrated a significant reduction in spike-wave discharge after the ESM was burst released from the chip under the same magnetic induction as in-vitro, indicating the potential application of the drug delivery chip. The flexible and membrane-like drug delivery chip utilizes drug-carrying magnetic nanoparticles as the building blocks that ensure a rapid and precise response to magnetic stimulus. Moreover, the flexible chip may offer advantages over conventional drug delivery devices by improvement of dosing precision, ease of operation, wider versatility of elution pattern, and better compliance. (C) 2009 Elsevier B.V. All rights reserved.
A Multifunctional Nanodevice Capable of Imaging, Magnetically Controlling, and In Situ Monitoring Drug Release
(2009-11-09)
Hu, Shang-Hsiu
;
Kuo, Kuan-Ting
;
Tung, Wei-Lin
;
Liu, Dean-Mo
;
Chen, San-Yuan
The multifunctional nanodevice described here integrates nanoscaled imaging, targeting, and controlled drug delivery, as well as the capability to monitor, in situ, the amount of drug released from the nanodevice with single-cell resolution. The nanodevice is composed of a polymer core/single-crystal iron oxide shell nanostructure bonded to a quantum dot. It shows outstanding release and retention characteristics via an external on/off manipulation of a high-frequency magnetic field. Upon magnetic stimulation, the single-crystal iron oxide shell demonstrates formation of nanometer-sized polycrystal domains of varying orientation. This allows a variation between retention and slow release of the drug. Further stimulation causes permanent rupturing of the shell, causing release of the drug in a burst-like manner. The quantum dot bonded to the nanodevice provides optical information for in situ monitoring of the drug release through use of a magnetic field. Remote control drug release from the nanodevice in a cancerous cell line (HeLa) was successfully accomplished using the same induction scenario. When nanodevices equipped with quantum dots are taken into cancerous cells, they are able to provide real-time drug dose information through a corresponding variation in emission spectrum. The nanodevice designed in this study has achieved its potential as a cell-based drug-delivery system for therapeutic applications.
A novel multifunctional nano-platform with enhanced anti-cancer and photoacoustic imaging modalities using gold-nanorod-filled silica nanobeads
(2013)
Chen, Po-Jung
;
Hu, Shang-Hsiu
;
Fan, Chih-Tai
;
Li, Meng-Lin
;
Chen, You-Yin
The novel nano-seaurchin structure is characteristic of high-density and well-dispersed gold nanorods in one mesoporous silica nanobead. This nanoplatform provided increased photothermal stability, stable photoacoustic signal and highly efficient hyperthermia effect both in vitro and in vivo, indicating a powerful theranostic modality.
An NAD(P)H: quinone oxidoreductase 1 (NQO1) enzyme responsive nanocarrier based on mesoporous silica nanoparticles for tumor targeted drug delivery in vitro and in vivo
(2016)
Gayam, Srivardhan Reddy
;
Venkatesan, Parthiban
;
Sung, Yi-Ming
;
Sung, Shuo-Yuan
;
Hu, Shang-Hsiu
The synthesis and characterization of an NAD(P)H: quinone oxidoreductase 1 (NQO1) enzyme responsive nanocarrier based on mesoporous silica nanoparticles (MSNPs) for on-command delivery applications has been described in this paper. Gatekeeping of MSNPs is achieved by the integration of mechanically interlocked rotaxane nanovalves on the surface of MSNPs. The rotaxane nanovalve system is composed of a linear stalk anchoring on the surface of MSNPs, an alpha-cyclodextrin ring that encircles it and locks the payload "cargo" molecules in the mesopores, and a benzoquinone stopper incorporated at the end of the stalk. The gate opening and controlled release of the cargo are triggered by cleavage of the benzoquinone stopper using an endogenous NQO1 enzyme. In addition to having efficient drug loading and controlled release mechanisms, this smart biocompatible carrier system showed obvious uptake and consequent release of the drug in tumor cells, could selectively induce the tumor cell death and enhance the capability of inhibition of tumor growth in vivo. The controlled drug delivery system demonstrated its use as a potential theranostic material.
Arrayed rGOSH/PMASH Microcapsule Platform Integrating Surface Topography, Chemical Cues, and Electrical Stimulation for Three-Dimensional Neuron-Like Cell Growth and Neurite Sprouting
(2014-06-01)
Liu, Heng-Wen
;
Huang, Wei-Chen
;
Chiang, Chih-Sheng
;
Hu, Shang-Hsiu
;
Liao, Chia-Hsin
The biocompatible thiol-functionalized rGOSH/PMASH microcapsules encapsulating nerve growth factor (NGF) are arrayed onto a transparent and conductive substrate, i.e., indium tin oxide (ITO), to integrate electrically stimulated cellular differentiation, electrically controlled NGF release, and topographically rough nano-surfaces into a 3-D platform for nerve regeneration. The rGOSH/PMASH microcapsules with microscale topography function not only as an adhesive coating to promote the adhesion of PC12 cells but also as electroactive NGF-releasing electrodes that stimulate NGF release and accelerate the differentiation of PC12 cells during electrical stimulation. Once electrical treatment is applied, NGF release and electrically enhanced cellular differentiation lead to an obvious increase both in the percentage of cells with neurites and in the neurite length. This length can reach nearly 90 m within 2 days of cell culture. The average neurite length is significantly increased (four-fold) after culture on the rGOSH/PMASH microcapsule substrate for 2 days compared with culture on a substrate without an rGOSH/PMASH coating. These multifunctional rGOSH/PMASH microcapsules may be used as potential 3-D patterned substrates for neural regeneration and neural prosthetics in tissue engineering applications.
Biomedical nanoparticle carriers with combined thermal and magnetic responses
(2009-02-01)
Liu, Ting-Yu
;
Hu, Shang-Hsiu
;
Liu, Dean-Mo
;
Chen, San-Yuan
;
Chen, I-Wei
Several biocompatible polymers are capable of large responses to small temperature changes around 37 degrees C In water, their responses include shrinkage and swelling as well as transitions in wettability. These properties have been harnessed for biomedical applications such as tissue engineering scaffolds and drug delivery carriers. A soft material/hard material hybrid in which a magnetic: metal or oxide is embedded in a temperature-responsive polymer matrix can combine the thermal sensitivity with magnetic signatures. Importantly, nanosizing such construct brings about new desirable features of extremely fast thermal response time, small magnetic hysteresis and enhanced magnetic susceptibility. Remote magnetic maneuvering and heating of the hybrid nanocolloids makes possible such applications as high-throughput enzyme separation and cell screening. Robust drug release on demand may also be obtained using these colloids and nanoparticle-derived thin film devices of combined thermal magnetic sensitivity. (C) 2008 Elsevier Ltd. All rights reserved.
Biomimetic nano-surfactant stabilizes sub-50 nanometer phospholipid particles enabling high paclitaxel payload and deep tumor penetration
(2018-10-01)
Choi, Hoon
;
Liu, Ting
;
Qiao, Hui
;
Chacko, Ann-Marie
;
Hu, Shang-Hsiu
Sub-50 nm nanoparticles feature long circulation and deep tumor penetration. However, at high volume fractions needed for intravenous injection, safe, highly biocompatible phospholipids cannot form such nanoparticles due to the fluidity of phospholipid shells. Here we overcome this challenge using a nano-surfactant, a sterilized 18-amino-acid biomimetic of the amphipathic helical motif abundant in HDL-apolipoproteins. As it induces a nanoscale phase (glass) transition in the phospholipid monolayer, the peptide stabilizes 5-7 nm phospholipid micelles that do not fuse at high concentrations but aggregate into stable micellesomes exhibiting size-dependent penetration into tumors. In mice bearing human Her-2-positive breast cancer xenografts, high-payload paclitaxel encapsulated in 25 nm (diameter) micellesomes kills more cancer cells than paclitaxel in standard clinical formulation, as evidenced by the enhanced apparent diffusion coefficient of water determined by in vivo MR imaging. Importantly, the bio-inertness of this biomimetic nano-surfactant spares the nanoparticles from being absorbed by liver hepatocytes, making them more generally available for drug delivery. (C) 2018 Elsevier Ltd. All rights reserved.
Characterization and drug release behavior of highly responsive chip-like electrically modulated reduced graphene oxide-poly(vinyl alcohol) membranes
(2012)
Liu, Heng-Wen
;
Hu, Shang-Hsiu
;
Chen, Yu-Wei
;
Chen, San-Yuan
;
材料科學與工程學系
"Hybrid hydrogel membranes composed of reduced graphene oxide (rGO) nanosheets and a poly (vinyl alcohol) (PVA) matrix were investigated as an electrically responsive drug release system. The rGO nanosheets in the matrix act as a physical barrier to inhibit the release of the model anesthetic drug, lidocaine hydrochloride, but the highly responsive release can be enhanced by the presence of rGO when exposed to an electrical stimulus. More interestingly, the on-demand drug release profiles of the assembled rGO-PVA hydrogel into a chip-like device can be highly controlled by an external electrical field. Release profiles ranging from a slow-elution pattern to a rapid release under electrical field treatment can be achieved by manipulating the rGO-PVA composition. Moreover, under cyclic exposure to an electrical stimulus, a highly controllable and repeatedly pulsatile release with desirable precision is obtained from the rGO-PVA hydrogel, implying that the hydrogel exhibits excellent anti-fatigue properties. By combining with the enhanced structural integrity and biocompatibility, the electrically responsive rGO-PVA hydrogel has demonstrated potential biological applications in drug delivery systems. In addition, the easy loading of hydrophilic drugs into the rGO-PVA hydrogel opens up a promising future in biological applications, such as transdermal therapy and wound healing."
Controlled pulsatile drug release from a ferrogel by a high-frequency magnetic field
(2007-09-18)
Hu, Shang-Hsiu
;
Liu, Ting-Yu
;
Liu, Dean-Mo
;
Chen, San-Yuan
;
材料科學與工程學系
Controlled Rupture of Magnetic Polyelectrolyte Microcapsules for Drug Delivery
(2008-10-21)
Hu, Shang-Hsiu
;
Tsai, Chia-Hui
;
Liao, Chen-Fu
;
Liu, Dean-Mo
;
Chen, San-Yuan
In this study, a magnetic-sensitive microcapsule was prepared using Fe3O4/poly(allylamine) (Fe3O4/PAH) polyelectrolyte to construct the shell. Structural integrity, microstructural evolution, and corresponding release behaviors of fluorescence dyes and doxorubicin were systematically investigated. Experimental observations showed that the presence of the magnetic nanoparticles in the shell structure allowed the shell structure to evolve from nanocavity development to final rupture of the shell under a given magnetic stimulus of different time durations. Such a microstructural evolution of the magnetic sensitive shell structure explained a corresponding variation of the drug release profile, from relatively slow release to burst-like behavior at different stages of stimulus. It has proposed that the presence of magnetic nanoparticles produced heat, due to magnetic energy dissipation (as Brown and Neel relaxations), and mechanical vibration and motion that induced stress development in the thin shell. Both mechanisms significantly accelerated the relaxation of the shell structure, causing such a microstructural evolution. With such a controllable microstructural evolution of the magnetic-sensitive shell structure, active substances can be well-regulated in a manageable manner with a designable profile according to the time duration under magnetic field. A cell culture study also indicated that the magnetic-sensitive microcapsules allowed a rapid uptake by the A549 cell line, a cancerous cell line, suggesting that the magnetic-sensitive microcapsule with controllable rupturing behavior of the shell offers a potential and effective drug carrier for anticancer applications.
Core-shell magnetic nanoparticles of heparin conjugate as recycling anticoagulants
(2007-12-01)
Liu, Ting-Yu
;
Huang, Li-Ying
;
Hu, Shang-Hsiu
;
Yang, Ming-Chien
;
Chen, San-Yuan
Polyvinyl alcohol-shell magnetic nanoparticles (PVA-shell MNPs, PMNPs) were successfully prepared by in-situ co-precipitation process. Heparin (HEP) was then covalently conjugated on the PMNPs by using aminotrimethoxysilane (ATMS) and 4,4-diphenyl methane diisocyanate (HMDI) as molecular coupling agent (spacer). The morphology of the core-shell PMNPs was examined using transmission electron microscope (TEM), X-ray diffraction (XRD), and Raman spectrometry to demonstrate the core-shell structure, as well as X-ray photoelectron spectroscope (X-PS) to provide direct evidence that the heparin molecules were immobilized on the surface of the core-shell PMNPs. Anticoagulant activity was evaluated with several parameters including activated partial thrombin time (APTT), prothrombin time (PT), fibrinogen time (FT), and thrombin time (TT). The results show that longer spacer would give better anticoagulant activity since lower steric hindrance can induce higher heparin grafting density. It might be anticipated that PMNPs of heparin conjugate can be used as anticoagulants instead of traditional free heparin, owing to its recycling characteristics by magnetic fields.
Core-Shell Nanocapsules Stabilized by Single-Component Polymer and Nanoparticles for Magneto-Chemotherapy/Hyperthermia with Multiple Drugs
(1970-01-01)
Hu, Shang-Hsiu
;
Liao, Bang-Jie
;
Chiang, Chin-Sheng
;
Chen, Po-Jung
;
Chen, I-Wei
Core/single-crystal-shell nanospheres for controlled drug release via a magnetically triggered rupturing mechanism
(2008-07-17)
Hu, Shang-Hsiu
;
Chen, San-Yuan
;
Liu, Dean-Mo
;
Hsiao, Chi-Sheng
;
材料科學與工程學系
Core/single-crystal-shell nanospheres are constructed from a poly-(N-vinyl2-pyrrolidone) (PVP)-modified silica core with an outer layer of single-crystal iron oxide shell. The nanospheres show outstanding release- and-zero-release characteristics via the addition and removal, respectively, of an external high-frequency magnetic field.
Drug Delivery Nanodevice, its Preparation Method and Uses Thereof
(2011-01-20)
Chen, San-Yuan
;
Hu, Shang-Hsiu
;
Liu, Dean-Mo
;
Kuo, Kun-Ting
Nanodevice and method for in vivo monitoring and release of drugs are provided. The disclosed nanodevice is characterized in having a drug-loaded nanosphere that is capable of releasing the encapsulated drugs upon magnetically stimulation. The nanodevice may also be used as a contrast agent for in vivo imaging and monitoring the concentration and distribution of the released drugs and/or active compounds injected separately into a target site of a subject.
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.
Enhancement of cancer therapy efficacy by trastuzumab-conjugated and pH-sensitive nanocapsules with the simultaneous encapsulation of hydrophilic and hydrophobic compounds
(2014-01-01)
Chiang, Chih-Sheng
;
Hu, Shang-Hsiu
;
Liao, Bang-Jie
;
Chang, Yuan-Ching
;
Chen, San-Yuan
Trastuzumab-conjugated pH-sensitive double emulsion nanocapsules (DENCs) stabilized by a single-component Poly (vinyl alcohol) (PVA) with magnetic nanoparticles can be fabricated through a two-step double emulsion process; these nanocapsules can be used to encapsulate hydrophilic doxorubicin (Dox) and hydrophobic paclitaxel (PTX) simultaneously. When PMA(SH) was attached to the shell of the DENCs, enhanced dual drug release of PTX/Dox was detected, specifically in intracellular acidic pH environments. The targeting ability of these Trastuzumab-conjugated DENCs was demonstrated with confocal images, which revealed a significantly elevated cellular uptake in HER-2 overexpressing SkBr3 cells. More importantly, an intravenous injection of this co-delivery system followed by magnetic targeting (MT) chemotherapy suppressed cancer growth in vivo more efficiently than the delivery of either PTX or Dox alone. The integration of the functionalities makes this combination therapy system a powerfully new tool for in vitro/in vivo cancer therapy, especially for in HER-2 positive cancers. From the Clinical Editor: Trastuzumab-conjugated pH-sensitive nanocapsules were used in this study for simultaneous targeted delivery of hydrophobic (PTX) and hydrophilic (Dox) anti-cancer agents to HER-2 positive cancer cells. Additional use of magnetic targeting demonstrated superior efficacy of this delivery system compared to PTX or Dox alone. (C) 2014 Elsevier Inc. All rights reserved.
Functionalized graphene nanocomposites for enhancing photothermal therapy in tumor treatment
(2016-10-01)
Chen, Yu-Wei
;
Su, Yu-Lin
;
Hu, Shang-Hsiu
;
Chen, San-Yuan
;
材料科學與工程學系
Graphene and its derivatives have unique physical and chemical properties that make them promising vehicles for photothermal therapy (PTT)-based cancer treatment. With intrinsic near-infrared (NIR) absorption properties, graphene-based nanomaterials can be used for PTT and other therapeutics, particularly in combination therapy, to provide successful thermal ablation of cancer cells. In the recent years, advances in graphene-based PTT have produced efficient and efficacious tumor inhibition via nanomaterial structural design and different functionalizations of graphene-derived nanocomposites. Graphene-based nanosystems exhibit multifunctional properties that are useful for PTT applications including enhancement of multimodalities, guided imaging, enhanced chemotherapy and low-power efficient PTT for optimum therapeutic efficiency. Therefore, in this review, we address critical issues and future aspects of PTT-based combination therapy. (C) 2016 Elsevier B.V. All rights reserved.
Geometrical confinement of quantum dots in porous nanobeads with ultraefficient fluorescence for cell-specific targeting and bioimaging
(2012)
Chen, Po-Jung
;
Hu, Shang-Hsiu
;
Hung, Wen-Ting
;
Chen, San-Yuan
;
Liu, Dean-Mo
In this study, a new imaging mesoporous nanoparticle is reported with exceptionally efficient and stable fluorescence emission, which was constructed by embedding and stabilizing quantum dots (QDs) of different sizes into porous nanobeads, following a lipid-PEG(2000)-COOH coating which was further encoded with cRGD targeting peptide through biotin-streptavidin bridges. The mesopores had similar to 10 nm diameter, were chemically modified, and facilitated internalization and stabilization of the QDs within the nanobeads upon the preparation protocol. Their outstanding optical contrasts render the highly fluorescent QDs as ideal fluorophores for wavelength-and-intensity multiplex color coding. The QDs tagged nanobeads showed optically strong and chemically stable imaging capability, both in vitro and in vivo, indicating powerful contrast modality among other alternatives. The cRGD-encoded lipid coated QDs tagged nanobeads (cRGD-encoded LQNBs) exhibited significantly increased alpha(v)beta(3)-expressing cell targeting toward MCF-7 breast cancer cells over the alpha(v)beta(3)-low expressing in HeLa cervix cancer cells, as confirmed by confocal laser scanning microscopy and flow cytometry. In MCF-7 xenograft nude mice, the cRGD-encoded LQNBs revealed prolonged accumulation time at the tumor site. In addition, the QNBs also demonstrated relatively high cell viability as compared to 3-mercaptopropionic acid (MPA)-functionalized QDs, indicating a successful design of highly-cytocompatible nanoparticulate platform capable of providing cell-specific targeting and nano-imaging modalities for biomedical applications.
Instantaneous Drug Delivery of Magnetic/Thermally Sensitive Nanospheres by a High-Frequency Magnetic Field
(2008-12-02)
Liu, Ting-Yu
;
Hu, Shang-Hsiu
;
Liu, Kun-Ho
;
Shaiu, Ren-Shiuan
;
Liu, Dean-Mo
Novel dual-functional nanospheres composed of magnetic iron oxide nanoparticles embedded in a thermo-sensitive Pluronic F127 (17127) matrix were successfully synthesized by an in situ coprecipitation process. The nanospheres were characterized by X-ray diffraction, transmission electron microscopy, X-ray photoelectron spectroscopy, and Raman spectroscopy. Experimental observations indicated that the F127 was subjected to a rapid structural change when the magnetic phase caused rapid heating after a short exposure to a high-frequency magnetic field. During the field duration, considerable volume shrinkage of the nanospheres (2.3-fold diameter reduction) was detected. This has been translated to an instantaneous release of a drug, Doxorubicin (DOX), when the DOX was encapsulated within the nanospheres. Such a rapidly responsive release of the DOX from the nanospheres was due to an intimate contact between the nanomagnet and F127, where an effective thermal and mechanical transfer between core and shell phases efficiently took place in the presence of the magnetic field.
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.