Publications by authors named "Narufumi Kitamura"

21 Publications

  • Page 1 of 1

The anti-angiogenic agent lenvatinib induces tumor vessel normalization and enhances radiosensitivity in hepatocellular tumors.

Med Oncol 2021 Apr 21;38(6):60. Epub 2021 Apr 21.

Department of Medical Physics, Graduate School of Medicine, Tohoku University, 2-1 Seiryo-machi, Aoba-ku, Sendai, 980-8575, Japan.

The evaluation of angiogenesis inhibitors requires the analysis of the precise structure and function of tumor vessels. The anti-angiogenic agents lenvatinib and sorafenib are multi-target tyrosine kinase inhibitors that have been approved for the treatment of hepatocellular carcinoma (HCC). However, the different effects on tumor vasculature between lenvatinib and sorafenib are not well understood. In this study, we analyzed the effects of both drugs on vascular structure and function, including vascular normalization, and investigated whether the normalization had a positive effect on a combination therapy with the drugs and radiation using micro X-ray computed tomography with gold nanoparticles as a contrast agent, as well as immunohistochemical analysis and interstitial fluid pressure (IFP) measurement. In mice subcutaneously transplanted with mouse HCC cells, treatment with lenvatinib or sorafenib for 14 days inhibited tumor growth and reduced the tumor vessel volume density. However, analysis of integrated data on vessel density, rates of pericyte-covering and perfused vessels, tumor hypoxia, and IFP measured 4 days after drug treatment showed that treatment with 3 mg/kg of lenvatinib significantly reduced the microvessel density and normalized tumor vessels compared to treatment with 50 mg/kg of sorafenib. These results showed that lenvatinib induced vascular normalization and improved the intratumoral microenvironment in HCC tumors earlier and more effectively than sorafenib. Moreover, such changes increased the radiosensitivity of tumors and enhanced the effect of lenvatinib and radiation combination therapy, suggesting that this combination therapy is a powerful potential application against HCC.
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http://dx.doi.org/10.1007/s12032-021-01503-zDOI Listing
April 2021

Development of X-ray contrast agents using single nanometer-sized gold nanoparticles and lactoferrin complex and their application in vascular imaging.

Colloids Surf B Biointerfaces 2021 Apr 1;203:111732. Epub 2021 Apr 1.

Department of Medical Physics, Graduate School of Medicine, Tohoku University, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8575, Japan; International Center for Synchrotron Radiation InnovationSmart (SRIS), Tohoku University, 2-1-1, Katahira, Aoba-ku, Sendai 980-8577, Japan. Electronic address:

The technology to accurately image the morphology of tumor vessels with X-ray contrast agents is important to clarify mechanisms underlying tumor progression and evaluate the efficacy of chemotherapy. However, in clinical practice, iodine-based contrast agents present problems such as short blood retention owing to a high clearance ability and insufficient X-ray absorption capacity when compared with other high atomic number elements. To resolve these issues, gold nanoparticles (AuNPs), with a high atomic number, have attracted a great deal of attention as contrast agents for angiography, and have been employed in small animal models. Herein, we developed novel contrast agents using AuNPs and captured changes in tumor vessel morphology with time using X-ray computed tomography (CT). First, glutathione-supported single nanometer-sized AuNPs (sAu/GSH) (diameter, 2.2 nm) were fabricated using tetrakis(hydroxymethyl)phosphonium chloride as a reducing agent. The sAu/GSH particles were intravenously injected into mice, remained in vessels for a few minutes, and were then excreted by the kidneys after 24 h, similar to the commercial contrast agent iopamidol. Next, the Au/GSH and lactoferrin (sAu/GSH-LF) (long axis size, 17.3 nm) complex was produced by adding lactoferrin to the sAu/GSH solution under the influence of a condensing agent. On intravenously administering sAu/GSH-LF to mice, the blood retention time was 1-3 h, which was considerably longer than that observed with iopamidol and sAu/GSH. Moreover, we succeeded in imaging morphological changes in identical tumor vessels for several days using X-ray CT with sAu/GSH-LF.
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http://dx.doi.org/10.1016/j.colsurfb.2021.111732DOI Listing
April 2021

[Supporting Technology for Development of Antibody Drug and Diagnostic Method to Predict Response to the Drug, by Using Fluorescence Imaging].

Gan To Kagaku Ryoho 2021 Feb;48(2):170-175

Dept. of Medical Physics, Graduate School of Medicine, Tohoku University.

Fluorescence imaging is a very useful method for visualizing molecules and cells, but when tissues are measured", decrease in resolution due to increased scattering and absorption of light in proportion to tissue thickness (problem 1)" and "decrease in signal to noise(S/N)ratio of positive signal due to tissue autofluorescence(problem 2)"are problems to be solved. In this paper, to develop a technology to improve the analysis accuracy of drug efficacy mechanisms in preclinical trial of drug discovery, we performed development of a supporting technology for drug discovery of antibody drug conjugates by imaging living tumor tissues, while solving problem 1. This technology is expected to lead to an improvement in the success rate of clinical trials. Next, to develop a diagnostic method to predict the response to neoadjuvant chemotherapy with antibody drugs for breast cancer, we performed development of fluorescence imaging of pathological tissues using fluorescent nanoparticles with ultra-high brightness, while solving problem 2. This diagnostic technology makes it possible to evaluate the expression level of the target protein of antibody drug with high quantitative and wide range sensitivity. This improved the accuracy of drug efficacy prediction. Therefore, patients who are expected to have a low drug efficacy will be able to select anticancer drugs with different mechanisms of action. These results of this study showed the reduction of drug discovery costs and improvement of individualized medicine. Thus, this study will greatly contribute to the development of precision medicine.
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February 2021

Heterogeneous Drug Efficacy of an Antibody-Drug Conjugate Visualized Using Simultaneous Imaging of Its Delivery and Intracellular Damage in Living Tumor Tissues.

Transl Oncol 2020 Jun 11;13(6):100764. Epub 2020 May 11.

Department of Breast and Endocrine Surgical Oncology, Graduate School of Medicine, Tohoku University, Sendai, Miyagi 980-8574, Japan.

Anticancer drug efficacy varies because the delivery of drugs within tumors and tumor responses are heterogeneous; however, these features are often more homogenous in vitro. This difference makes it difficult to accurately determine drug efficacy. Therefore, it is important to use living tumor tissues in preclinical trials to observe the heterogeneity in drug distribution and cell characteristics in tumors. In the present study, to accurately evaluate the efficacy of an antibody-drug conjugate (ADC) containing a microtubule inhibitor, we established a cell line that expresses a fusion of end-binding protein 1 and enhanced green fluorescent protein that serves as a microtubule plus-end-tracking protein allowing the visualization of microtubule dynamics. This cell line was xenografted into mice to create a model of living tumor tissue. The tumor cells possessed a greater number of microtubules with plus-ends, a greater number of meandering microtubules, and a slower rate of microtubule polymerization than the in vitro cells. In tumor tissues treated with fluorescent dye-labeled ADCs, heterogeneity was observed in the delivery of the drug to tumor cells, and microtubule dynamics were inhibited in a concentration-dependent manner. Moreover, a difference in drug sensitivity was observed between in vitro cells and tumor cells; compared with in vitro cells, tumor cells were more sensitive to changes in the concentration of the ADC. This study is the first to simultaneously evaluate the delivery and intracellular efficacy of ADCs in living tumor tissue. Accurate evaluation of the efficacy of ADCs is important for the development of effective anticancer drugs.
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http://dx.doi.org/10.1016/j.tranon.2020.100764DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7218300PMC
June 2020

Automated Quantification of Extranuclear ERα using Phosphor-integrated Dots for Predicting Endocrine Therapy Resistance in HR/HER2 Breast Cancer.

Cancers (Basel) 2019 Apr 12;11(4). Epub 2019 Apr 12.

Department of Medical Physics, Graduate School of Medicine, Tohoku University, Sendai, Miyagi 980-8574, Japan.

In addition to genomic signaling, Estrogen receptor alpha (ERα) is associated with cell proliferation and survival through extranuclear signaling contributing to endocrine therapy (ET) resistance. However, the relationship between extranuclear ERα and ET resistance has not been extensively studied. We sought to measure extranuclear ERα expression by immunohistochemistry using phosphor-integrated dots (IHC-PIDs) and to assess its predictive value for ET resistance. After quantitative detection of ERα by IHC-PIDs in vitro, we developed "the nearest-neighbor method" to calculate the extranuclear ERα. Furthermore, tissue sections from 65 patients with HR+/HER2- BC were examined by IHC-PIDs, and the total ERα, nuclear ERα, extranuclear ERα PIDs score, and ratio of extranuclear-to-nuclear ERα (ENR) were measured using the novel method. We demonstrate that quantification of ERα using IHC-PIDs exhibited strong correlations to real-time qRT-PCR ( = 0.94) and flow cytometry ( = 0.98). High ERα ENR was significantly associated with poor overall survival ( = 0.048) and disease-free survival (DFS) ( = 0.007). Multivariate analysis revealed that the ERα ENR was an independent prognostic factor for DFS [hazard ratio, 3.8; 95% CI, 1.4-11.8; = 0.006]. Our automated measurement has high accuracy to localize and assess extranuclear ERα. A high ERα ENR in HR/HER2 BC indicates decreased likelihood of benefiting from ET.
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http://dx.doi.org/10.3390/cancers11040526DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6520781PMC
April 2019

Quantitative analyses of amount and localization of radiosensitizer gold nanoparticles interacting with cancer cells to optimize radiation therapy.

Biochem Biophys Res Commun 2019 01 12;508(4):1093-1100. Epub 2018 Dec 12.

Department of Medical Physics, Graduate School of Medicine, Tohoku University, Sendai, Miyagi, 980-8575, Japan. Electronic address:

Previous studies showed that gold nanoparticles (AuNPs) are useful radiosensitizers which optimize radiation therapy under low-dose radiation. However, the mechanisms of AuNP radiosensitization, including the amount and localization of the AuNPs interacting with cancer cells, has not yet been quantified. To answer these questions, we prepared AuNPs conjugated with anti-human epidermal growth factor receptor type 2 (HER2) antibody via polyethylene glycol (PEG) chains (AuNP-PEG-HER2ab). AuNP-PEG-HER2ab specifically bound to the HER2-expressing cancer cells and entered the cells via endocytosis. Whether endocytosis of AuNP-PEG-HER2ab occurred had no effect on radiosensitization efficacy by AuNP-PEG-HER2ab in vitro. The radiosensitization efficacy in vitro depended on dose of AuNP-PEG-HER2ab or dose of X-ray. Moreover, AuNP-PEG-HER2ab administrated into tumor-bearing mice was localized to both the periphery of the tumor tissue and near the nuclei in cancer cells in tumor deep tissue. The localization of AuNP-PEG-HER2ab in tumor tissues was important factors for in vivo powerful radiosensitization efficacy.
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http://dx.doi.org/10.1016/j.bbrc.2018.12.016DOI Listing
January 2019

X-ray computed tomography imaging of a tumor with high sensitivity using gold nanoparticles conjugated to a cancer-specific antibody via polyethylene glycol chains on their surface.

Sci Technol Adv Mater 2016 26;17(1):387-397. Epub 2016 Jul 26.

Department of Nano-Medical Science, Graduate School of Medicine, Tohoku University, Sendai, Japan; Department of Surgical Oncology, Graduate School of Medicine, Tohoku University, Sendai, Japan.

Contrast agents are often used to enhance the contrast of X-ray computed tomography (CT) imaging of tumors to improve diagnostic accuracy. However, because the iodine-based contrast agents currently used in hospitals are of low molecular weight, the agent is rapidly excreted from the kidney or moves to extravascular tissues through the capillary vessels, depending on its concentration gradient. This leads to nonspecific enhancement of contrast images for tissues. Here, we created gold (Au) nanoparticles as a new contrast agent to specifically image tumors with CT using an enhanced permeability and retention (EPR) effect. Au has a higher X-ray absorption coefficient than does iodine. Au nanoparticles were supported with polyethylene glycol (PEG) chains on their surface to increase the blood retention and were conjugated with a cancer-specific antibody via terminal PEG chains. The developed Au nanoparticles were injected into tumor-bearing mice, and the distribution of Au was examined with CT imaging, transmission electron microscopy, and elemental analysis using inductively coupled plasma optical emission spectrometry. The results show that specific localization of the developed Au nanoparticles in the tumor is affected by a slight difference in particle size and enhanced by the conjugation of a specific antibody against the tumor.
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http://dx.doi.org/10.1080/14686996.2016.1194167DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5101864PMC
July 2016

Quantitative diagnosis of HER2 protein expressing breast cancer by single-particle quantum dot imaging.

Cancer Med 2016 10 26;5(10):2813-2824. Epub 2016 Sep 26.

Department of Surgical Oncology, Graduate School of Medicine, Tohoku University, Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan.

Overexpression of HER2 is one of the major causes of breast cancer, and therefore precise diagnosis of its protein expression level is important. However, current methods estimating the HER2-expression level are insufficient due to problem with the lack of quantification. This might result in a gap between diagnostics and therapeutics targeting HER2. Therefore, a new effective diagnostic method is needed. We developed a new immunohistochemical (IHC) technique with quantum dots (QD)-conjugated trastuzumab using single-particle imaging to quantitatively measure the HER2 expression level. Tissues from 37 breast cancer patients with available detailed clinical information were tested by IHC with QDs (IHC-QD) and the correlation with IHC with 3,3'-diaminobenzidine (DAB), fluorescence in situ hybridization (FISH), and IHC-QD was examined. The number of QD-conjugated trastuzumab particles binding specifically to a cancer cell was precisely calculated as the IHC-QD score. The IHC-QD score in 37 cases was correlated proportionally with the score of HER2 gene copy number as assessed by FISH (R = 0.83). When HER2 positivity was judged to be positive, the IHC-QD score with our cut-off level was exactly concordant with the FISH score with a cut-off value of 2.0. Furthermore, IHC-QDs score and time to progression (TTP) of trastuzumab therapy were well correlated in HER2-positive cases (R = 0.69). Conversely, the correlation between FISH score and TTP was not observed. We developed a precisely quantitative IHC method using trastuzumab-conjugated QDs and single-particle imaging analysis and propose the possibility of using IHC-QDs score as a predictive factor for trastuzumab therapy.
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http://dx.doi.org/10.1002/cam4.898DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5083734PMC
October 2016

Interaction between cells and poly(ethylene glycol)-lipid conjugates.

Colloids Surf B Biointerfaces 2015 Nov 22;135:765-773. Epub 2015 Aug 22.

Department of Reparative Materials, Institute for Frontier Medical Sciences, Kyoto University, 53 Kawahara-Cho, Shogoin, Sakyo-Ku, Kyoto 606-8507, Japan. Electronic address:

Eight types of poly(ethylene glycol)-lipid(PEG-lipids) carrying different lipid tails were synthesized. These PEG-lipids were labeled with fluorescein isothiocyanate (FITC-PEG-lipids) to examine their interaction with cells and to quantitatively determine amounts of PEG-lipids bound on the cell surface. FITC-PEG-lipids spontaneously anchored to the cell membrane within 15 min without loss of cell viability. The type of lipid had very little effect on the anchoring rates, while an increase in the hydrophobicity of the lipid portion of the PEG-lipids slowed their dissociation rates. Densities of FITC-PEG-lipids on the cell surface ranged from 1 × 10(-3) to 1 × 10(-2)molecules/nm(2), depending on the kinds of lipids employed. The relationship between the stability of the lipids on the cell membrane and the hydrophobicity of the lipid moieties will give a basis for the selection of a hydrophobic moiety in PEG-lipid conjugates for use in specific applications.
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http://dx.doi.org/10.1016/j.colsurfb.2015.08.014DOI Listing
November 2015

A DNA hybridization system for labeling of neural stem cells with SPIO nanoparticles for MRI monitoring post-transplantation.

Biomaterials 2015 Jun 3;54:158-67. Epub 2015 Apr 3.

Institute for Frontier Medical Sciences, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan. Electronic address:

Neural stem cells (NSCs) demonstrate encouraging results in cell replacement therapy for neurodegenerative disorders and traumatic injury in the central nervous system. Monitor the survival and migration of transplanted cells would provide us important information concerning the performance and integration of the graft during the therapy time course. Magnetic resonance imaging (MRI) allow us to monitor the transplanted cells in a non-invasive way. The only requirement is to use an appropriate contrast agent to label the transplanted cells. Superparamagnetic iron oxide (SPIO) nanoparticles are one of the most commonly used contrast agent for MRI detection of transplanted cells. SPIO nanoparticles demonstrated to be suitable for labeling several types of cells including NSCs. However, the current methods for SPIO labeling are non-specific, depending mostly on electrostatic interactions, demanding relatively high SPIO concentration, and long incubation time, which can affect the viability of cells. In this study, we propose a specific and relatively fast method to label NSCs with SPIO nanoparticles via DNA hybridization. Two short single stranded DNAs (ssDNAs), oligo[dT]20 and oligo[dA]20 were conjugated with a lipid molecule and SPIO nanoparticle respectively. The labeling process comprises two simple steps; first the cells are modified to present oligo[dT]20 ssDNA on the cell surface, then the oligo[dA]20 ssDNA conjugated with SPIO nanoparticles are presented to the modified cells to allow the oligo[dT]20-oligo[dA]20 hybridization. The method showed to be non-toxic at concentrations up to 50 μg/mL oligo[dA]20-SPIO nanoparticles. Presence of SPIO nanoparticles at cell surface and cell cytoplasm was verified by transmission electron microscopy (TEM). SPIO labeling via DNA hybridization demonstrated to not interfere on NSCs proliferation, aggregates formation, and differentiation. NSCs labeled with SPIO nanoparticles via DNA hybridization system were successfully detected by MRI in vitro as well in vivo. Cells transplanted into the rat brain striatum could be detected by MRI scanning up to 1 month post-transplantation.
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http://dx.doi.org/10.1016/j.biomaterials.2015.03.017DOI Listing
June 2015

Labeling of islet cells with iron oxide nanoparticles through DNA hybridization for highly sensitive detection by MRI.

Bioorg Med Chem 2013 Nov 7;21(22):7175-81. Epub 2013 Sep 7.

Institute for Frontier Medical Sciences, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.

A labeling method for islet cells with superparamagnetic iron oxide nanoparticles (SPIOs) based on DNA hybridization is proposed for monitoring of transplanted islets by magnetic resonance imaging (MRI). The surfaces of SPIOs were modified by via Michael reaction by reacting oligo-(deoxyadenylic acid)-bearing a terminal thiol group at the 5'-end ((dA)20-SH) with maleic acid functional groups on the SPIOs. The SPIOs were immobilized on islet cells which had been pretreated with oligo-(thymidylic acid)-poly(ethylene glycol)-phospholipid conjugates ((dT)20-PEG-DPPE) through DNA hybridization. Transmission electron microscopy observations revealed that SPIOs were initially anchored on the islet cell surfaces and subsequently transferred to endosomes or exfoliated with time. The SPIO-labeled islet cells could be clearly detected as dark spots by T2(*)-weighted MR image, whereas non-labeled islet cells could not be detected.
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http://dx.doi.org/10.1016/j.bmc.2013.08.063DOI Listing
November 2013

Heat-initiated detection for reduced glutathione with ¹⁹F NMR probes based on modified gold nanoparticles.

Bioorg Med Chem Lett 2013 Jan 1;23(1):281-6. Epub 2012 Nov 1.

Department of Polymer Chemistry, Graduate School of Engineering, Kyoto University, Katsura, Nishikyo-ku, Kyoto 615-8510, Japan.

For detecting reduced glutathione (GSH) with a (19)F NMR spectroscopy with time-specificity, we developed the probes based on gold nanoparticles modified with the fluorinated groups via the thermally-cleavable linkers. Before the heating treatment with the probe, the maleimide moiety as a binding site with GSH in the probe is inactivated by cycloaddition of furan. At this silent state, the magnitude of (19)F NMR signals from the fluorinated groups was suppressed. By heating for the activation of the probe, the maleimide moiety was produced via retro Diels-Alder reaction, and (19)F NMR signals were observed. From this moment, GSH started the reaction with the probe via Michael addition to the maleimide moiety, leading to the observation of the new peak in (19)F NMR spectra. Finally, the amounts of GSH were determined from the increase of the magnitude of (19)F NMR signals.
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http://dx.doi.org/10.1016/j.bmcl.2012.10.105DOI Listing
January 2013

Reduced glutathione-resisting ¹⁹F NMR sensors for detecting HNO.

Bioorg Med Chem 2012 Aug 15;20(15):4668-74. Epub 2012 Jun 15.

Department of Polymer Chemistry, Graduate School of Engineering, Kyoto University, Katsura, Nishikyo-ku, Kyoto 615-8510, Japan.

The (19)F NMR probes for the HNO detection are reported. We synthesized the probe molecules with the paramagnetic Cu(II) complex and fluorine atoms using a cubic silsesquioxane. By using the magnetism changes of the Cu(II) to Cu(I) in the complex by the reduction with HNO, the (19)F NMR signal intensities of the probe increased. Noteworthily, our probes have superior resistance to reduced glutathione which is the major intracellular molecule to maintain the reductive environment and the competitor in the reduction of Cu(II) against HNO.
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http://dx.doi.org/10.1016/j.bmc.2012.06.013DOI Listing
August 2012

Heavy metal-free 19F NMR probes for quantitative measurements of glutathione reductase activity using silica nanoparticles as a signal quencher.

Bioorg Med Chem 2012 Jan 23;20(1):96-100. Epub 2011 Nov 23.

Department of Polymer Chemistry, Graduate School of Engineering, Kyoto University, Katsura, Nishikyo-ku, Kyoto 615-8510, Japan.

For the quantitative assessment of the glutathione reductase (GR) activity with a (19)F NMR spectroscopy, we developed the heavy metal-free probes based on silica nanoparticles modified with water-soluble perfluorinated dendrimers via the disulfide linkers. Before enzymatic reaction, the molecular rotation of the perfluorinated dendrimers is highly restricted, and the magnitude of (19)F NMR signals from the perfluorinated dendrimers can be suppressed. By the reductive cleavage of the disulfide linkers with the reduced glutathione-mediated enzymatic reaction of GR, perfluorinated dendrimers can be released from the surfaces of the nanoparticles. Consequently, the (19)F NMR signals of perfluorinated dendrimers were recovered. The enzymatic activity of GR was determined from the increase of the magnitude of (19)F NMR signals. Finally, to demonstrate the feasibility of the probe in the presence of miscellaneous molecules under bio-mimetic conditions, the comparison study was executed with the cancer cell lysate. The value determined from our method showed a good agreement with that from the conventional method.
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http://dx.doi.org/10.1016/j.bmc.2011.11.026DOI Listing
January 2012

Bimodal quantitative monitoring for enzymatic activity with simultaneous signal increases in 19F NMR and fluorescence using silica nanoparticle-based molecular probes.

Bioconjug Chem 2011 Aug 11;22(8):1484-90. Epub 2011 Jul 11.

Department of Polymer Chemistry, Graduate School of Engineering, Kyoto University, Katsura, Nishikyo-ku, Kyoto 615-8510, Japan.

We describe the bimodal quantitative assay for enzymatic activity in (19)F NMR spectroscopy and fluorescence spectroscopy using a nanoparticle-based molecular probe. Perfluorinated dendrimers were tethered on silica nanoparticles with a phosphate-caged fluorescein as a linker. Before enzymatic reaction, the molecular rotation of the perfluorinated dendrimers should be highly restricted, and the (19)F NMR signals from the perfluorinated dendrimers were too broad to be detected relative to the noise level. Fluorescence signals of fluorescein were suppressed by the presence of the diphosphate groups. Following the enzymatic reaction with an alkaline phosphatase, perfluorinated dendrimers and fluorescein were released, and the NMR signals of perfluorinated dendrimers and strong fluorescence from fluorescein were correspondingly observed. The enzymatic activity and reaction rates of the hydrolysis of alkaline phosphatase were detected from the increases of fluorescence and (19)F NMR signals. Finally, the feasibility of the probe in the presence of miscellaneous molecules under biomimetic conditions was demonstrated by determining of the enzymatic activity in cell lysate. Quantitative analysis using both (19)F NMR spectroscopy and fluorescence spectroscopy can be accomplished.
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http://dx.doi.org/10.1021/bc100381xDOI Listing
August 2011

Preparation for highly sensitive MRI contrast agents using core/shell type nanoparticles consisting of multiple SPIO cores with thin silica coating.

Langmuir 2010 Jul;26(14):11759-62

Department of Polymer Chemistry, Graduate School of Engineering, Kyoto University, Katsura, Nishikyo-ku, Kyoto 615-8510, Japan.

We describe here the facile and robust preparation methods for the multiple-SPIO-containing silica-coated core/shell type nanoparticles which can serve as a highly sensitive MRI contrast agent. The imidazolium-tethered core/shell type particles were synthesized, and the centrifugal selection for the multiple-SPIO-containing particles and the etching process to fabricate thin silica layers were carried out to improve the proton relaxivity of water tissue. We found that the synthetic particles can provide approximately 7-fold clearer contrasts than that of the particles before treatments. In addition, the particles can show good dispersibility at least for 1 week in aqueous media.
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http://dx.doi.org/10.1021/la1015077DOI Listing
July 2010

Acceleration of guanine oxidation under visible light irradiation by photon upconversion based on triplet-triplet annihilation.

Nucleic Acids Symp Ser (Oxf) 2009 (53):183-4

Department of Polymer Chemistry, Graduate School of Engineering, Kyoto University, Katsura, Kyoto 615-8510, Japan.

We report the fluorescent polymer complex which can show fluorescence emission at 380 nm with the excitation of 520 nm in aqueous media. This photon upconversion based on triplet-triplet annihilation can efficiently take place via inter-molecular energy transfers between the Ru complex as a sensitizer and anthracene molecules as an emitter captured into the water-soluble network polymers. We performed the oxidation reaction of 2'-deoxyguanosine by riboflavin in the presence of the polymer complex with the visible light irradiation. It was clearly indicated that oxidative decomposition can be accelerated by UV light generation via upconversion based on triplet-triplet annihilation.
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http://dx.doi.org/10.1093/nass/nrp092DOI Listing
May 2010

Reversible signal regulation system of 19F NMR by redox reactions using a metal complex as a switching module.

Bioorg Med Chem 2009 Jun 24;17(11):3818-23. Epub 2009 Apr 24.

Department of Polymer Chemistry, Graduate School of Engineering, Kyoto University, Katsura, Nishikyo-ku, Kyoto 615-8510, Japan.

We present here the reversible signal regulation of (19)F NMR using the transition metal complex as a switching module. Water-soluble fluorinated dendrimers containing ferrocene were synthesized as a probe, and the signal intensities of (19)F NMR of the probes were monitored by changing the valence state of the ferrocene moiety. By oxidation of the ferrocene moiety, the relaxation of the nearby fluorine atoms was accelerated via the paramagnetic relaxation enhancement, as a result the (19)F NMR signal from the probe was significantly decreased. The reduction of the ferrocenium cation of the probe recovered the signal intensity. Finally, in combination with the difference of the fluorescence quenching ability between ferrocene and ferrocenium cation, we constructed the multimodal (19)F NMR/fluorescence probe based on the redox switching system.
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http://dx.doi.org/10.1016/j.bmc.2009.04.039DOI Listing
June 2009

Multi-modal 19F NMR probe using perfluorinated cubic silsesquioxane-coated silica nanoparticles for monitoring enzymatic activity.

Chem Commun (Camb) 2008 Dec 21(46):6176-8. Epub 2008 Oct 21.

Department of Polymer Chemistry, Graduate School of Engineering, Kyoto University, Katsura, Nishikyo-ku, Kyoto, 615-8510, Japan.

The establishment of (19)F NMR signal regulation and the application of this strategy to develop a multi-modal (19)F NMR probe for monitoring enzymatic activity using nanoparticles as a signal regulator is described; water-soluble perfluorinated cubic silsesquioxane was synthesized and immobilized onto the silica nanoparticles for suppressing the signals; (19)F NMR signals of the probes were recovered by releasing from nanoparticles.
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http://dx.doi.org/10.1039/b815022bDOI Listing
December 2008

Assembly system of direct modified superparamagnetic iron oxide nanoparticles for target-specific MRI contrast agents.

Bioorg Med Chem Lett 2008 Oct 11;18(20):5463-5. Epub 2008 Sep 11.

Department of Polymer Chemistry, Graduate School of Engineering, Kyoto University, Katsura, Nishikyo-ku, Kyoto 615-8510, Japan.

We report the direct modification of SPIOs with a biomolecule and the target-specific assembly system of these modified SPIOs for using MRI contrast agents. The transverse relaxation rate of the aqueous solutions containing the modified SPIOs was altered by the dispersion state.
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http://dx.doi.org/10.1016/j.bmcl.2008.09.035DOI Listing
October 2008

Properties of superparamagnetic iron oxide nanoparticles assembled on nucleic acids.

Nucleic Acids Symp Ser (Oxf) 2008 (52):693-4

Department of Polymer Chemistry, Graduate School of Engineering, Kyoto University, Nishikyoku, Kyoto 615-8510, Japan.

We report the direct modification of SPIOs with a biomolecule, and the sequence-specific assembly of the modified SPIOs was achieved with the aptamer-small molecule interaction. In addition, the transverse relaxation rate of the aqueous solutions containing the modified SPIOs was altered by the dispersion state.
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http://dx.doi.org/10.1093/nass/nrn350DOI Listing
November 2010