Browsing by Author "Liau, Ian"

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Assessment of the In Vivo Toxicity of Gold Nanoparticles
(2009-08-01)
Chen, Yu-Shiun
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Hung, Yao-Ching
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Liau, Ian
;
Huang, G. Steve
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材料科學與工程學系
The environmental impact of nanoparticles is evident; however, their toxicity due to their nanosize is rarely discussed. Gold nanoparticles (GNPs) may serve as a promising model to address the size-dependent biological response to nanoparticles because they show good biocompatibility and their size can be controlled with great precision during their chemical synthesis. Naked GNPs ranging from 3 to 100 nm were injected intraperitoneally into BALB/C mice at a dose of 8 mg/kg/week. GNPs of 3, 5, 50, and 100 nm did not show harmful effects; however, GNPs ranging from 8 to 37 nm induced severe sickness in mice. Mice injected with GNPs in this range showed fatigue, loss of appetite, change of fur color, and weight loss. Starting from day 14, mice in this group exhibited a camel-like back and crooked spine. The majority of mice in these groups died within 21 days. Injection of 5 and 3 nm GNPs, however, did not induce sickness or lethality in mice. Pathological examination of the major organs of the mice in the diseased groups indicated an increase of Kupffer cells in the liver, loss of structural integrity in the lungs, and diffusion of white pulp in the spleen. The pathological abnormality was associated with the presence of gold particles at the diseased sites, which were verified by ex vivo Coherent anti-Stoke Raman scattering microscopy. Modifying the surface of the GNPs by incorporating immunogenic peptides ameliorated their toxicity. This reduction in the toxicity is associated with an increase in the ability to induce antibody response. The toxicity of GNPs may be a fundamental determinant of the environmental toxicity of nanoparticles.
Characterization of the Mechanodynamic Response of Cardiomyocytes with Atomic Force Microscopy
(2013-02-05)
Chang, Wei-Tien
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Yu, David
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Lai, Yu-Cheng
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Lin, Kuen-You
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Liau, Ian
Characterization of the Mechanodynamic Response of Cardiomyocytes with Atomic Force Microscopy
Characterization of the Pharmaceutical Effect of Drugs on Atherosclerotic Lesions in Vivo Using Integrated Fluorescence Imaging and Raman Spectral Measurements
(2014-04-15)
Yang, Yi-Cyun
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Chang, Wei-Tien
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Huang, Shao-Kang
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Liau, Ian
;
應用化學系
Direct assessment of the vascular lesions of model animals in vivo is important for the development of new antiatherosclerotic drugs. Nevertheless, biochemical analysis of the lipid profile in blood in vitro remains the most common way to evaluate the therapeutic effect of drugs targeting atherosclerosis because of an inherent difficulty to access the vascular wall. Using hypercholesterolemic zebrafish, we present an orchestrated application of Raman spectral measurements and confocal fluorescence imaging to interrogate the pharmacological response of atherosclerotic lesions in situ and in vivo. For demonstration, we investigated two commonly prescribed antihyperlipidemic drugs, ezetimibe and atorvastatin. The treatment of ezetimibe or atorvastatin alone decreased effectively the deposition of lipids in the vascular wall, and a combined dose showed a synergistic effect. Atorvastatin exerted a profound antioxidative effect on vascular fatty lesions. Analysis of individual lesions shows further that these lesions exhibited a heterogeneous response to the treatment of atorvastatin; a significant fraction of, but not all, the lesions became nonoxidized after the intervention. Beyond its efficacies in suppressing both the accumulation and oxidation of vascular lipids, atorvastatin expedited the clearance of vascular lipids. The possession of pleotropic (multiple) therapeutic effects on vascular fatty lesions of hypercholesterolemic zebrafish by atorvastatin is notably consistent with the known pharmaceutical effects of this drug on human beings. These results improve our understanding of the antiatherosclerotic effect of drugs. We envisage that our approach has the potential to become a platform to predict the pharmaceutical effects of new drugs aiming to cure human atherosclerotic diseases.
CNS-targeted AAV5 gene transfer results in global dispersal of vector and prevention of morphological and function deterioration in CNS of globoid cell leukodystrophy mouse model
(2011-08-01)
Lin, Dar-Shong
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Hsiao, Chung-Der
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Liau, Ian
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Lin, Shuan-Pei
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Chiang, Ming-Fu
Globoid cell leukodystrophy (GLD) is a devastating lysosomal storage disease caused by deficiency of the enzyme galactocerebrosidase (GALC). Currently, there is no definite cure for GLD. Several attempts with CNS-directed gene therapy in twitcher mice (a murine model of GLD) demonstrated restricted expression of GALC activity in CNS and failure of therapeutic efficacy in cerebellum and spinal cord, resulting in various degrees of correction of biochemical, pathological and clinical phenotype. More recently, twitcher mice receiving a combination of hematopoietic and viral vector gene transfer therapies were not protected from neurodegeneration and axonopathy in both cerebellum and spinal cord. This evidence indicates the requirement of sufficient and widespread GALC expression in CNS and rescue of cerebellum and spinal cord in the therapeutic intervention of murine model of GLD. In this study, we have optimized intracranial delivery of AAV2/5-GALC to the neocortex, hippocampus and cerebellum, instead of the thalamus as was previously conducted, of twitcher mice. The CNS-targeted AAV2/5 gene transfer effectively dispersed GALC transgene along the neuraxis of CNS as far as the lumbar spinal cord, and reduced the accumulation of psychosine in the CNS of twitcher mice. Most importantly, the treated twitcher mice were protected from loss of oligodendrocytes and Purkinje cells, axonopathy and marked gliosis, and had significantly improved neuromotor function and prolonged lifespan. These preclinical findings with our approach are encouraging, although a more robust response in the spinal cord would be desirable. Collectively, the information in this study validates the efficacy of this gene delivery approach to correct enzymatic deficiency, psychosine accumulation and neuropathy in CNS of GLD. Combining cell therapy such as bone marrow transplantation with treatment with the aim of reducing inflammation, replacing dead or dying oligodendrocytes and targeting PNS may provide a synergistic and more complete correction of this disease. (C) 2011 Elsevier Inc. All rights reserved.
Confocal Imaging Guided Photochemical Thrombosis Toward the Development of a Novel Zebrafish Model of Stroke
(2016-01-01)
Lee, I-Ju
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Hsu, Jia-Wen
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Chuang, Yung-Jen
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Liau, Ian
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生物科技學系
Confocal imaging guided photochemical thrombosis was demonstrated on living zebrafish. Occlusion at selected cerebral blood vessels caused varied mortality rate and neurological outcome. This novel zebrafish stroke model may facilitate translational research and thrombolytic screening.
Controllable NO release from Cu1.6S nanoparticle decomposition of S-nitrosoglutathiones following photothermal disintegration of polymersomes to elicit cerebral vasodilatory activity
(2017-01-01)
Kao, Po-Tsung
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Lee, I-Ju
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Liau, Ian
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Yeh, Chen-Sheng
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交大名義發表
Since the discovery of nitric oxide (NO) as a vasodilator, numerous NO therapies have been attempted to remedy disorders related to pathological vasoconstriction such as coronary artery disease. Despite the advances, clinical applications of NO therapies remain limited mainly because of the low stability of molecular NO donors (and NO molecules), and concerns about the increased oxidative stress and reduced arterial pressure associated with the systemic administration of NO. Here we design a photo-responsive polymersome with nitrosothiols and Cu1.6S nanoparticles in its core and shell, respectively, and demonstrate the photo-triggered release of NO and its vasodilatory activity on zebrafish. Unlike conventional approaches, our design enhances the stability of NO donors and prospectively enables spatiotemporal regulation of NO release, thus minimizing the harmful effects associated with conventional NO therapies. We anticipate that such a strategy will open up new clinical applications of NO and help reveal the complex biological effects of NO in vivo.
Doxorubicin-Loaded Nanosized Micelles of a Star-Shaped Poly(epsilon-Caprolactone)-Polyphosphoester Block Co-polymer for Treatment of Human Breast Cancer
(2011)
Nguyen-Van Cuong
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Hsieh, Ming-Fa
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Chen, Yung-Tsung
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Liau, Ian
;
應用化學系
Star-shaped co-polymers based on the backbone of poly(epsilon-caprolactone) were synthesized by a ring-opening reaction using pentaerythritol as initiator and Sn(Oct)(2) as catalyst. The star-shaped poly(epsilon-caprolactone) polymer was then chain extended with a terminal block of poly(ethyl ethylene phosphate) to form a copolymer, poly(epsilon-caprolactone)-poly(ethyl ethylene phosphate), when using the cyclic ethyl ethylene phosphate monomer. The amphiphilic block co-polymers can self-assemble into nanoscopic micelles with a mean diameter of 150 nm and a spherical shape. Additionally, the prepared micelles did not induce hemolysis and nitric oxide production in vitro based on nitric oxide, hemolytic tests and MTT assays. The hydrophobic micellar cores encapsulated doxorubicin (DOX) in an aqueous solution with a loading efficiency of 55.2%. The in vitro release of DOX from DOX-loaded micelles was pH dependent. DOX-loaded micelles present significantly enhanced cytotoxicity to both MCF-7/drug-sensitive and MCF-7/drug-resistant cells after second incubation. Moreover, results of confocal microscopy and flow cytometry of DOX-loaded micelles demonstrate the feasibility of this delivery system for effective therapy of drug-resistant tumours. (C) Koninklijke Brill NV, Leiden, 2011
Enhanced optical confinement of dielectric nanoparticles by two-photon resonance transition
(2017-01-01)
Kittiravechote, Aungtinee
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Usman, Anwar
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Masuhara, Hiroshi
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Liau, Ian
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應用化學系
Despite a tremendous success in the optical manipulation of microscopic particles, it remains a challenge to manipulate nanoparticles especially as the polarizability of the particles is small. With a picosecond-pulsed near-infrared laser, we demonstrated recently that the confinement of dye-doped polystyrene nanobeads is significantly enhanced relative to bare nanobeads of the same dimension. We attributed the enhancement to an additional term of the refractive index, which results from two-photon resonance between the dopant and the optical field. The optical confinement is profoundly enhanced as the half-wavelength of the laser falls either on the red side, or slightly away from the blue side, of the absorption band of the dopant. In contrast, the ability to confine the nanobeads is significantly diminished as the half-wavelength of the laser locates either at the peak, or on the blue side, of the absorption band. We suggest that the dispersively shaped polarizability of the dopant near the resonance is responsible to the distinctive spectral dependence of the optical confinement of nanobeads. This work advances our understanding of the underlying mechanism of the enhanced optical confinement of doped nanoparticles with a nearinfrared pulsed laser, and might facilitate future research that benefits from effective sorting of selected nanoparticles beyond the limitations of previous approaches.
Fluorescent tracer of dopamine enables selective labelling and interrogation of dopaminergic amacrine cells in the retina of living zebrafish
(2016-01-01)
Lin, Hui-Jen
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Hong, Zhen-Yi
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Li, Yaw-Kuen
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Liau, Ian
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生物科技學系
The retinal dopaminergic amacrine cell plays multiple roles in vision; it optimizes the encoding of visual stimuli, serves as an output of the circadian rhythm, and influences trophic processes. Specific identification of such cells in vivo remains challenging. A fluorescent tracer that mimics natural dopamine would help elucidate the distribution and the functional roles of dopaminergic neurons. Here we report a fluorescent tracer of dopamine for the selective labeling and study of retinal dopaminergic amacrine cells in vivo. This tracer has low toxicity and effective selectivity, and enables fluorescent determination of the evoked release of dopamine and the femtosecond laser ablation of single dopaminergic amacrine cells in living zebrafish. Our approach is readily adaptable by other research groups, and is expected to accelerate biomedical research in domains related to the pathophysiology of retinal dopaminergic amacrine cells.
Gold nanoparticles caused learning impairment in mice
(2009)
Chen, Yu-Shiun
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Hung, Yao-Ching
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Liau, Ian
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Lin, Li-Wei
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Hong, Meng-Yeng
Aims : To investigate the toxic effect of gold nanoparticles (GNPs) to the learning and memory of mice. Main methods: Naked GNPs of 17 nm and 37 nm were synthesized, purified, and injected intraperitoneally into BALB/C mice at a dose of 8 mg/kg/week. Passive avoidance test was performed to detect the possible leaning impairment. Biochemical analysis to examine levels of monoamine and acetylcholine in mouse brain was also performed. ICP-MS was performed to examine the presence of GNP in brain. Localization of GNP at hippocampus was surveyed by ex vivo Coherent anti-Stoke Raman scattering (CARS) microscopy. Transmission electron microscopy (TEM) was also performed to verify the cellular location of GNPs at hippocampus. Key findings: Both 17 nm and 37 nm GNPs induced severe sickness in rnice. However, only 17 rim GNP impaired the learning and memory of mice. GNP treatment elevated levels of dopamine from 114.5 ng/mouse brain to 143.6 ng/mouse brain for 17 nm (p<0.01) and to 138.2 for 37 nm GNP (p<0.05). Serotinin was significantly reduced by 17 nm GNP treatment from 57.2 ng/mouse brain to 44.3 ng/mouse brain (p<0.05). ICP-MS indicated the presence of GNPs in every part of the brain. CARS microscopy showed that 17 nm GNP was located at the Cornu Amonis regions of hippocampus where neuronal cells clustered, while 37 nm GNP was excluded from the cell clustered region. TEM and EDAX verified the presence of 17 nm GNP in the cytoplasm and in the dendrite of pyramidal cell, while 37 rim GNP was found in the extracellular region of neuronal cells. TEM image also indicated that both endocytosis and free diffusion coexisted for the invasion of 17 nm GNP. Significance: The current study provided evidence that nanoparticles were capable of entering into brain and affecting normal brain function. The size-dependent invading ability of GNPs provides an extra dimension for drug delivery.
Imaging of Zebrafish In Vivo with Second-Harmonic Generation Reveals Shortened Sarcomeres Associated with Myopathy Induced by Statin
(2011-09-23)
Huang, Shih-Hao
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Hsiao, Chung-Der
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Lin, Dar-Shong
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Chow, Cho-Yen
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Chang, Chia-Jen
We employed second-harmonic generation (SHG) imaging and the zebrafish model to investigate the myopathy caused by statin in vivo with emphasis on the altered microstructures of the muscle sarcomere, the fundamental contractile element of muscles. This approach derives an advantage of SHG imaging to observe the striated skeletal muscle of living zebrafish based on signals produced mainly from the thick myosin filament of sarcomeres without employing exogenous labels, and eliminates concern about the distortion of muscle structures caused by sample preparation in conventional histological examination. The treatment with statin caused a significantly shortened sarcomere relative to an untreated control (1.73 +/- 0.09 mu m vs 1.91 +/- 0.08 mu m, P<0.05) while the morphological integrity of the muscle fibers remained largely intact. Mechanistic tests indicated that this microstructural disorder was associated with the biosynthetic pathway of cholesterol, or, specifically, with the impaired production of mevalonate by statins. This microstructural disorder exhibited a strong dependence on both the dosage and the duration of treatment, indicating a possibility to assess the severity of muscle injury according to the altered length of the sarcomeres. In contrast to a conventional assessment of muscle injury using clinical biomarkers in blood, such as creatine kinase that is released from only disrupted myocytes, the ability to determine microstructural modification of sarcomeres allows diagnosis of muscle injury before an onset of conventional clinical symptoms. In light of the increasing prevalence of the incidence of muscle injuries caused by new therapies, our work consolidates the combined use of the zebrafish and SHG imaging as an effective and sensitive means to evaluate the safety profile of new therapeutic targets in vivo.
Induction of Cell-Cell Connections by Using in situ Laser Lithography on a Perfluoroalkyl-Coated Cultivation Platform
(2011-03-21)
Okano, Kazunori
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Yu, David
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Matsui, Ai
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Maezawa, Yasuyo
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Hosokawa, Yoichiroh
This article describes a novel laser-directed microfabrication method carried out in aqueous solution for the organization of cell networks on a platform. A femtosecond (fs) laser was applied to a platform culturing PC12, HeLa, or normal human astrocyte (NHA) cells to manipulate them and to facilitate mutual connections. By applying an fs-laser-induced impulsive force, cells were detached from their original location on the plate, and translocated onto microfabricated cell-adhesive domains that were surrounded with a cell-repellent perfluoroalkyl (R(f)) polymer. Then the fs-laser pulse-train was applied to the Rf polymer surface to modify the cell-repellent surface, and to make cell-adhesive channels of several mm in width between each cell-adhesive domain. PC12 cells elongated along the channels and made contact with others cells. HeLa and NHA cells also migrated along the channels and connected to the other cells. Surface analysis by X-ray photoelectron spectroscopy (XPS) and atomic force microscopy (AFM) confirmed that the Rf polymer was partially decomposed. The method presented here could contribute not only to the study of developing networks of neuronal, glial, and capillary cells, but also to the quantitative analysis of nerve function.
Integrated multiple multi-photon imaging and Raman spectroscopy for characterizing structure-constituent correlation of tissues
(2008-10-13)
Jhan, Jhen-Wei
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Chang, Wei-Tien
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Chen, Hung-Che
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Lee, Yu-Tsung
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Wu, Ming-Fang
Histopathological imaging of tissues often requires extensive sample preparation including fixation and staining in order to highlight characteristic alterations associated with diseases. Herein, we report an integrated spectro-microscopy approach based on a combination of multimodal multi-photon imaging and Raman micro-spectroscopy and demonstrate label-free characterization of the structure-constituent correlation of porcine skin. The multi-modal imaging allows the visualization of dermatological features whereas Raman micro-spectroscopy enables the identification of their 'molecular fingerprints'. By obtaining both structural and molecular-level information of tissue constituents, this integrated approach can offer new insight into the patho-physiological status of tissues. (c) 2008 Optical Society of America
Interplay between Structure and Fluidity of Model Lipid Membranes under Oxidative Attack
(2010-12-02)
Tai, Wan-Yu
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Yang, Yi-Cyun
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Lin, Hui-Jen
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Huang, Chin-Ping
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Cheng, Yi-Lin
A proper regula:ion of membrane fluidity is critical for cellular activities such as communication between cells, mitosis, an :I endocytosis. Unsaturated lipids, a main component of biological membranes, are particularly susceptible to oxidative attack of reactive oxygen species. The oxidation of lipids can produce structural derangement of membranes and eventually alter the membrane fluidity. We have applied fluorescence correlation spectroscopy (FCS) and Raman spectroscopy to investigate the fluidity and structure of model membranes subject to oxidative attack. Hydrogen peroxide has little effect on the lateral fluidity of membranes. whereas hydroxyl radical causes a significantly increased fluidity. The latter is rationalized with the cleavage of the acyl chains of lipids caused by hydroxyl radical; this interpretation is founded on the diminished intensities of lines in Raman spectra associated with -CH(2) and C = C moieties in lipids and supported by mass-spectral measurements. The same approach provides a mechanistic account of the inhibitory capability of vitamins C and E against ate increased membrane fluidity resulting from an oxidative attack. Membranes with much cholesterol exhibit a novel resistance against altered membrane fluidity induced with oxidative attack; this finding has biological implications. Our approach combining FCS and Raman measurements reveals the interplay between the structure and fluidity of membranes and provides insight into the pathophysiology of cellular oxidative injury.
Intravital Imaging of Ischemia and Reperfusion
(2013)
Liau, Ian
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應用化學系
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Department of Applied Chemistry
Timely evaluation of specific pathogenic mechanisms that underlie ischemia-reperfusion injury is essential to improve our understanding of the pathogenesis and to help develop effective therapies. Herein we report employment of intravital microscopy to visualize ischemia and reperfusion of rat liver in real time in vivo. We show that the time-lapse autofluorescence images exhibited a unique spatiotemporal change during the time course of ischemia and reperfusion. The intensity decreased rapidly after ischemia, but recovered gradually during reperfusion, with a rate depending strongly on the duration of ischemia. The intravital imaging further enabled direct visualization of occlusion of local microcirculation and showed that it led to delayed reoxygenation of cells, a pathogenic mechanism that would inevitably contribute tissue damage. Supported with complimentary hypoxia-reoxygenation experiments and inhibitory assays performed on cultured hepatocytes, we conclude that the variation of autofluorescence is mechanistically linked with the conversion of mitochondrial flavoproteins between the non-fluorescent reduced state and fluorescent oxidized state.
Longitudinal and quantitative assessment platform for concurrent analysis of anti-tumor efficacy and cardiotoxicity of nano-formulated medication in vivo
(2020-01-25)
Tu, Wei-Ming
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Huang, Xin-Chun
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Chen, Yen-Ling
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Luo, Yun-Ling
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Liau, Ian
Increasing nanomedicinal approaches have been developed to effectively inhibit tumor growth; however, critical questions such as whether a nanomedicinal approach can mitigate latent side effects are barely addressed. To this end, we established a zebrafish xenograft tumor model, combining pseudodynamic three-dimensional cardiac imaging and image analysis to enable simultaneous and quantitative determination of the change of tumor volume and cardiac function of zebrafish upon specific nanoformulation treatment. Doxorubicin (DOX), a well-known chemotherapeutic agent with cardiotoxicity, and a recently developed DOX-loaded nanocomposite were employed as two model drugs to demonstrate the effectiveness to utilize the proposed evaluation platform for rapid validation. The nanoformulation significantly mitigated DOX-associated cardiotoxicity, while retaining the efficacy of DOX in inhibiting tumor growth compared to administration of carrier-free DOX at the same dose. We anticipate that this platform possesses the potential as an efficient assessment system for nanoformulated cancer therapeutics with suspected toxicity and side effects to vital organs such as the heart. (C) 2019 Elsevier B.V. All rights reserved.
Molecular Imaging of Ischemia and Reperfusion in Vivo with Mitochondria! Autofluorescence
(2014-05-20)
Lu, Hsueh-Han
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Wu, Yao-Ming
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Chang, Wei-Tien
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Luo, Teng
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Yang, Yi-Cyun
Ischemia and reperfusion (IR) injury constitutes a pivotal mechanism of tissue damage in pathological conditions such as stroke, myocardial infarction, vascular surgery, and organ transplant. Imaging or monitoring of the change of an organ at a molecular level in real time during IR is essential to improve our understanding of the underlying pathophysiology and to guide therapeutic strategies. Herein, we report molecular imaging of a rat model of hepatic IR with the autofluorescence of mitochondrial flavins. We demonstrate a revelation of the histological characteristics of a liver in vivo with no exogenous stain and show that intravital autofluorescent images exhibited a distinctive spatiotemporal variation during IR. The autofluorescence decayed rapidly from the baseline immediately after 20-min ischemia (approximately 30% decrease in 5 mm) but recovered gradually during reperfusion (to approximately 99% of the baseline 9 mm after the onset of reperfusion). The autofluorescent images acquired during reperfiision correlated strongly with the reperfused blood flow. We show further that the autofluorescence was produced predominantly from mitochondria, and the distinctive autofluorescent variation during IR was mechanically linked to the altered balance between the flavins in the oxidized and reduced forms residing in the mitochondrial electron-transport chain. Our approach opens an unprecedented route to interrogate the deoxygenation and reoxygenation of mitochondria, the machinery central to the pathophysiology of IR injury, with great molecular specificity and spatiotemporal resolution and can be prospectively translated into a medical device capable of molecular imaging. We envisage that the realization thereof should shed new light on clinical diagnostics and therapeutic interventions targeting IR injuries of not only the liver but also other vital organs including the brain and heart.
Morphological Stabilization by Supramolecular Perfl uorophenyl-C-60 Interactions Leading to Effi cient and Thermally Stable Organic Photovoltaics
(2014-03-01)
Liao, Ming-Hung
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Tsai, Che-En
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Lai, Yu-Ying
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Cao, Fong-Yi
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Wu, Jhong-Sian
A new PC61BM-based fullerene, [6,6]-phenyl-C-61 butyric acid pentafluorophenyl ester (PC61BPF) is designed and synthesized. This new n-type material can replace PC61BM to form a P3HT:PC61BPF binary blend or serve as an additive to form a P3HT:PC61BM:PC61BPF ternary blend. Supramolecular attraction between the pentafluorophenyl group of PC61BPF and the C-60 cores of PC61BPF/PC61BM can effectively suppress the PC61BPF/PC61BM materials from severe aggregation. By doping only 8.3 wt% PC61BPF, device PC(61)BP(F)651 exhibits a PCE of 3.88% and decreases slightly to 3.68% after heating for 25 h, preserving 95% of its original value. When PC61BP with non-fluorinated phenyl group is used to substitute PC61BPF, the stabilizing ability disappears completely. The efficiencies of PC(61)BP651 and PC(61)BP321 devices significantly decay to 0.44% and 0.11%, respectively, after 25 h isothermal heating. Most significantly, this strategy is demonstrated to be effective for a blend system incorporating a low band-gap polymer. By adding only 10 wt% PC61BPF, the PDTBCDTB:PC71BM-based device exhibits thermally stable morphology and device characteristics. These findings demonstrate that smart utilization of supramolecular interactions is an effective and practical strategy to control morphological evolution.
Multiphoton microscopy in defining liver function
(2014-09-01)
Thorling, Camilla A.
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Crawford, Darrell
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Burczynski, Frank J.
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Liu, Xin
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Liau, Ian
Multiphoton microscopy is the preferred method when in vivo deep-tissue imaging is required. This review presents the application of multiphoton microscopy in defining liver function. In particular, multiphoton microscopy is useful in imaging intracellular events, such as mitochondrial depolarization and cellular metabolism in terms of NAD(P) H changes with fluorescence lifetime imaging microscopy. The morphology of hepatocytes can be visualized without exogenously administered fluorescent dyes by utilizing their autofluorescence and second harmonic generation signal of collagen, which is useful in diagnosing liver disease. More specific imaging, such as studying drug transport in normal and diseased livers are achievable, but require exogenously administered fluorescent dyes. If these techniques can be translated into clinical use to assess liver function, it would greatly improve early diagnosis of organ viability, fibrosis, and cancer. (C) The Authors.
Oligonucleotides as 'bio-solvent' for in situ extraction and functionalisation of carbon nanoparticles
(2014-01-01)
Chen, Yu-Cheng
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Wen, Cheng-Che
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Liau, Ian
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Hsieh, You-Zung
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Hsu, Hsin-Yun
A simple yet novel one-pot approach is developed to prepare carbon nanoparticles with diameters of similar to 2 nm and modified by oligonucleotides. We use single-stranded deoxyribonucleic acid (ssDNA), which serves as a unique 'bio-solvent' for carbon nanoparticle (CNP) preparation and as a target molecule for functionalisation. Proposed interactions relevant to the stabilisation of the final oligonucleotide-CNP complex include pi-pi stacking and pi-HN bonding with sp(2) carbon atoms on the CNP surface. Furthermore, oligonucleotide-enriched CNPs can be readily extracted within seconds from a crude mixture of single-walled carbon nanotubes (SWCNTs) without any need for post-synthesis chemical modification. The established CNPs are biocompatible, possess intrinsic fluorescence, and do not result in the undesirable photobleaching effect, rendering them potential candidates for in vivo biological applications.