Browsing by Author "Liu, Tse-Ying"

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A theranostic nrGO@MSN-ION nanocarrier developed to enhance the combination effect of sonodynamic therapy and ultrasound hyperthermia for treating tumor
(2016)
Chen, Yu-Wei
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Liu, Tse-Ying
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Chang, Po-Hsueh
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Hsu, Po-Hung
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Liu, Hao-Li
Sonodynamic therapy (SDT), which induces activation of sonosensitizers in cancer cells through ultrasound irradiation, has emerged as an alternative and promising noninvasive therapeutic approach to kill both superficial and deep parts of tumors. In this study, mesoporous silica (MSN) grown on reduced graphene oxide nanosheet (nrGO) capped with Rose Bengal (RB)-PEG-conjugated iron-oxide nanoparticles (IONs), nrGO@MSN-ION-PEG-RB, was strategically designed to have targeted functionality and therapeutic efficacy under magnetic guiding and focused ultrasound (FUS) irradiation, respectively. The singlet oxygen produced by ultrasound-activated RB and the ultrasound-induced heating effect was enhanced by rGO and IONs, which improved the cytotoxic effect in cancer cells. In an animal experiment, we demonstrated that the combination of sonodynamic/hyperthermia therapy with magnetic guidance using this nanocomposite therapeutic agent can produce remarkable efficacious therapy in tumor growth inhibition. Furthermore, the combination effect induced by FUS irradiation produces significant damage to both superficial and deep parts of the targeted tumor.
Circulating tumor-cell-targeting Au-nanocage-mediated bimodal phototherapeutic properties enriched by magnetic nanocores
(2020-07-07)
Chiang, Chih-Sheng
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Kao, Yu-Che
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Webster, Thomas J.
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Shyu, Woei-Cherng
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Cheng, Hung-Wei
Metastasis resulting from circulating tumor cells (CTCs) is associated with 90% of all cancer mortality. To disrupt cancer dissemination, therapeutic targeting of CTCs by extracorporeal photodynamic therapy (PDT) has emerged; however, it still remains impractical due to its limited therapeutic window. Herein, we developed a photosensitive and magnetic targeted core-satellite nanomedicine (TCSN) to augment the light-induced damage to the targeted cells. The magnetic nanocore (MNC) with multiple iron oxide nanoparticles stabilized using thiolated polyvinyl alcohol can magnetize the CTCs to achieve magnetic enrichment under a magnetic field. Multiple gold nanocage (AuNC) satellites were conjugated on the MNC to facilitate bimodal photothermal therapy and PDT. Adjusting the thiol content in the MNC allows manipulating the AuNC density on TCSNs, which has been found to demonstrate a density-dependent bimodal phototherapeutic effect under laser irradiation at 808 and 940 nm. Moreover, with the immobilization of anti-epithelial cell adhesion molecule (anti-EpCAM), TCSN exhibited an enhanced affinity toward EpCAM-expressing 4T1 cells. We demonstrate that TCSN-labeled 4T1 cells can be isolated and photo-eradicated in a microfluidic channel with a dynamic flow. Our studies showed that TCSN with the complementary properties of MNC and AuNCs can largely augment the therapeutic window by magnetic enrichment and bimodal phototherapy, serving as an advanced extracorporeal strategy to remove CTCs.
Effect of hydroxyapatite nanoparticles on ibuprofen release from carboxymethyl-hexanoyl chitosan/O-hexanoyl chitosan hydrogel
(2006-09-01)
Liu, Tse-Ying
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Liu, Ting-Yu
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Chen, San-Yuan
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Chen, Shian-Chuan
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Liu, Dean-Mo
In order to explore the effect of nanofiller on the regulation of the drug release behavior from micro sphere-embedded hydrogel prepared by carboxymethyl-hexanoyl chitosan (HNOCC) and O-hexanoyl chitosan (OHC), the release kinetics was investigated in terms of various amounts of calcium-deficient hydroxyapatite (CDHA) nanoparticles incorporated. HNOCC is a novel chitosan-based hydrophilic matrix with a burst release profile in a highly swollen state. The drug release kinetics of the HNOCC hydrogel can be regulated by incorporation of well-dispersed CDHA nanoparticles. It was found that the release duration of ibuprofen (IBU) from HNOCC was prolonged with increasing amounts of CDHA which acts as a crosslink agent and diffusion barrier. On the contrary, the release duration of the IBU from OHC (hydrophobic phase) was shortened through increasing the CDHA amount over 5%, which is due to the hydrophilic nature of the CDHA nanoparticles destroying the intermolecular hydrophobic interaction and accelerating OHC degradation. Thus, water accessibility and molecular relaxation were enhanced, resulting in a higher release rate. In addition, sustained and sequential release behavior was achieved by embedding the OHC microspheres (hydrophobic phase) into the HNOCC (hydrophilic phase) matrix, which could significantly prolong the release duration of the HNOCC drug-loaded implant.
Growth factors-loaded calcium phosphate/polymer hybrid coating with sequential release behavior prepared via electrochemical deposition method
(2016-10-15)
Sar, Jenny I-Chun
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Lin, Yen-Zhu
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Lin, Chung-Kwei
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Liu, Tse-Ying
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Chen, San-Yuan
In this study, the dicalcium phosphate dehydrate (DCPD)/carboxymethyl hexanoyl chitosan (CHC) hybrid coating layer with sequential release of BMP-2 and TGF-beta 1 was deposited onto Ti6Al4V substrate by electrochemical co-precipitation method. Different concentrations of amphiphatic chitosan derivative (carboxymethyl hexanoyl chitosan, CHC), BMP-2 and TGF-beta 1-loaded PLA microspheres (PLA/TGF-beta 1 MSs) were co-precipitated with the precursor of DCPD. The resulting DCPD/CHC hybrid coating incorporated with BMP-2 and PLA/TGF-beta 1 MSs was designed for improving the osteoconductive and osteoinductive functionalities of Ti6Al4V. FTIR spectroscopy and X-ray diffraction were used to characterize these hybrid coatings. The drug release profile, MC3T3-E1 cell proliferation and alkaline phosphatase activity were used to investigate the functionality of these hybrid coatings. It was found that the incorporation of CHC could be used as a mean to manipulate the release behavior of growth factor from the DCPD/CHC hybrid coating. In addition, the BMP-2- and PLA/TGF-beta 1 MSs-incorporated DCPD/CHC hybrid coating exhibited a sequential release of BMP-2 and TGF-beta 1 during the first and second two weeks, respectively. Importantly, the DCPD/CHC hybrid coating immersed in simulated body fluid gradually transformed to hydroxyapatite phase. Hence, the BMP-2 and PLA/TGF-beta 1 MSs-incorporated DCPD/CHC hybrid coating exhibited the best cell viability and the highest ALP activity after 14 days. The biocompatible hybrid coating with sequential release functionality proposed in the present study can enhance the osseointegration process and possess promising potential for clinical applications in bone implants and tissue engineering. (C) 2016 Elsevier B.V. All rights reserved.
Growth factors-loaded calcium phosphate/polymer hybrid coating with sequential release behavior prepared via electrochemical deposition method
(2016-10-15)
Sar, Jenny I-Chun
;
Lin, Yen-Zhu
;
Lin, Chung-Kwei
;
Liu, Tse-Ying
;
Chen, San-Yuan
In this study, the dicalcium phosphate dehydrate (DCPD)/carboxymethyl hexanoyl chitosan (CHC) hybrid coating layer with sequential release of BMP-2 and TGF-beta 1 was deposited onto Ti6Al4V substrate by electrochemical co-precipitation method. Different concentrations of amphiphatic chitosan derivative (carboxymethyl hexanoyl chitosan, CHC), BMP-2 and TGF-beta 1-loaded PLA microspheres (PLA/TGF-beta 1 MSs) were co-precipitated with the precursor of DCPD. The resulting DCPD/CHC hybrid coating incorporated with BMP-2 and PLA/TGF-beta 1 MSs was designed for improving the osteoconductive and osteoinductive functionalities of Ti6Al4V. FTIR spectroscopy and X-ray diffraction were used to characterize these hybrid coatings. The drug release profile, MC3T3-E1 cell proliferation and alkaline phosphatase activity were used to investigate the functionality of these hybrid coatings. It was found that the incorporation of CHC could be used as a mean to manipulate the release behavior of growth factor from the DCPD/CHC hybrid coating. In addition, the BMP-2- and PLA/TGF-beta 1 MSs-incorporated DCPD/CHC hybrid coating exhibited a sequential release of BMP-2 and TGF-beta 1 during the first and second two weeks, respectively. Importantly, the DCPD/CHC hybrid coating immersed in simulated body fluid gradually transformed to hydroxyapatite phase. Hence, the BMP-2 and PLA/TGF-beta 1 MSs-incorporated DCPD/CHC hybrid coating exhibited the best cell viability and the highest ALP activity after 14 days. The biocompatible hybrid coating with sequential release functionality proposed in the present study can enhance the osseointegration process and possess promising potential for clinical applications in bone implants and tissue engineering. (C) 2016 Elsevier B.V. All rights reserved.
In situ synthesis of hybrid nanocomposite with highly order arranged amorphous metallic copper nanoparticle in poly(2-hydroxyethyl methacrylate) and its potential for blood-contact uses
(2008-11-01)
Liu, Yen-Yu
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Liu, Dean-Mo
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Chen, San-Yuan
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Tung, Tsan-Hua
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Liu, Tse-Ying
A hybrid consisting of a highly ordered nanostructure of metallic Cu(0) nanoparticles embedded in a poly(2-hydroxyethyl methacrylate) (pHEMA) matrix was successfully synthesized by in situ photopolymerization, followed by in situ chemical reduction. The evolution of an ordered nanostructure of Cu(0) showing a nearly amorphous nature is discussed, and it is proposed that it is due to a coupling interaction between the Cu precursor and the unpaired O of the COOR group, associated with water molecules, among pHEMA molecules. The hybrids showed a negative surface charge and considerable improvement in blood compatibility compared to neat pHEMA and the widely used biomaterial polysulfonate. (C) 2008 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
Magnetic-sensitive behavior of intelligent ferrogels for controlled release of drug
(2006-07-04)
Liu, Ting-Yu
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Hu, Shang-Hsiu
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Liu, Tse-Ying
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Liu, Dean-Mo
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Chen, San-Yuan
An intelligent magnetic hydrogel (ferrogel) was fabricated by mixing poly(vinyl alcohol) (PVA) hydrogels and Fe3O4 magnetic particles through freezing-thawing cycles. Although the external direct current magnetic field was applied to the ferrogel, the drug was accumulated around the ferrogel, but the accumulated drug was spurt to the environment instantly when the magnetic fields instantly switched "off". Furthermore, rapid to slow drug release can be tunable while the magnetic field was switched from "off" to "on" mode. The drug release behavior from the ferrogel is strongly dominated by the particle size of Fe3O4 under a given magnetic field. The best "magnetic-sensitive effects" are observed for the ferrogels with larger Fe3O4 particles due to its stronger saturation magnetization and smaller coercive force. Furthermore, the amount of drug release can be controlled by fine-tuning of the switching duration time (SDT) through an externally controllable on-off operation in a given magnetic field. It was demonstrated that the highest burst drug amounts and best "close" configuration of the ferrogel were observed for the SDT of 10 and 5 min, respectively. By taking these peculiar magnetic-sensitive characteristics of the novel ferrogels currently synthesized, it is highly expected to have a controllable or programmable drug release profile that can be designed for practical clinical needs.
Self-assembled hollow nanocapsule from amphiphatic carboxymethyl-hexanoyl chitosan as drug carrier
(2008-09-09)
Liu, Kun-Ho
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Chen, San-Yuan
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Liu, Dean-Mo
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Liu, Tse-Ying
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材料科學與工程學系
A new type of amphiphilic chitosan, which was synthesized through the use of both hydrophilic carboxymethyl and hydrophobic hexanoyl substitutions, was employed to self-assemble into a hollow nanocapsule in an aqueous environment. Critical aggregation concentration (cac) and zeta potential were experimentally identified for the amphiphilic chitosan (CHC). Both experimental data suggested that the self-assembly behavior of the CHC is fundamentally determined as an interplay between the hydrophobic interaction and the variation of the zeta potential upon hexanoyl substitution, which further influenced the nanostructural evolution of the nanocapsules. Higher hexanoyl substitution promoted larger nanocapsules, ca. 200 nm in diameter, while a reduced zeta potential was correspondingly detected, and vice versa, forming smaller nanocapsules, ca. 20 nm in diameter. The self-assemble mechanism, together with the corresponding nanostructural stability, of this unique CHC nanocapsule was also proposed in terms of intermolecular interaction and thermodynamic reason. By taking the advantage of the self-assemble (or self-aggregation) capability, the CHC was employed for drug encapsulation, i.e., doxorubicin, an anticancer molecule; we found in this preliminary evaluation that it reached an efficiency of 46.8%, and a corresponding drug release from the nanocapsules for a time period exceeded 7 days can be achieved in vitro.
Synthesis and characterization of amphiphatic carboxymethyl-hexanoyl chitosan hydrogel: Water-retention ability and drug encapsulation
(2006-11-07)
Liu, Tse-Ying
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Chen, San-Yuan
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Lin, Yi-g Lin
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Liu, Dean-Mo
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材料科學與工程學系
Carboxymethyl-hexanoyl chitosan (NOCHC) amphiphatic hydrogel with excellent water-absorption and water-retention abilities under neutral conditions was successfully synthesized for the first time and then employed as a carrier for delivering amphiphatic agents. NOCHCis a water-soluble chitosan derivative bearing the carboxymethyl (hydrophilic) group and the hexanoyl (hydrophobic) group, which was synthesized using N,O-carboxymethyl chitosan (NOCC) as the starting precursor. Water-absorption ability (W-c), water-retention ability, and drug encapsulation efficiency of the NOCHC hydrogel were investigated in terms of the degree of carboxymethyl and hexanoyl substitution. It was found that the amount of moisture uptake was dependent on the relative humidity as well as degree and nature of such substitution. The hexanoyl substitution affected significantly the water-absorption ability by altering the number of water-binding sites and the state of water under low humidity and the fully swollen state, respectively. In addition, the presence of hydrophobic hexanoyl substitution significantly retards water mobility during deswelling, causing better water-retention ability. Moreover, compared with that of pristine chitosan and NOCC, the encapsulation efficiency of ibuprofen (partially hydrophobic agent) was significantly enhanced with the incorporation of the hexanoyl group. These results demonstrate that the newly developed NOCHC amphiphatic hydrogel showed enhanced water-absorption ability, water-retention ability, and amphiphatic drug encapsulation efficiency compared with NOCC and chitosan.
Synthesis and characterization of nanoporous SiO2/pHEMA biocomposites
(2008-08-01)
Liu, Yen-Yu
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Liu, Tse-Ying
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Chen, San-Yuan
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Liu, Dean-Mo
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材料科學與工程學系
Porous SiO2/pHEMA biocomposites were synthesized in situ by incorporating silica nanoparticles with a hydroxyethyl methacrylate (HEMA) monomer, following a UV-induced photopolymerization. The nanostructure of the composites was characterized and the resulting physical properties were examined. The release kinetics of the model molecule-vitamin B12-and the hemocompatibility of the porous SiO2/pHEMA composites were investigated. Heterogeneous reaction kinetics is proposed to be the formation mechanism of the nanoporosity in the pHEMA matrix as a result of incorporating silica nanoparticles following photopolymerization. Experimental results also demonstrated that the incorporation of the silica nanoparticles into the pHEMA matrix not only enhanced the mechanical property but also maintained a good hemocompatibility of the resulting biocomposites. In addition, it was observed that the drug release profile of the composites (in the form of a membrane) can be precisely regulated from a two-stage pattern to one-stage pattern by varying the concentration of both the SiO2 nanoparticles and HEMA monomer during synthesis. The permeability of the model drug was enhanced by two orders of magnitude from 4.22 x10(-7) cm(2)/h to 3.92 x 10(-5) cm(2)/h by controlling the micro-to-nanostructure of the composites. The platelet adhesion experiment demonstrated low aggregation of the platelets on the surface of the biocomposite membranes, indicating a promising antithrombotic property.