Thi Kim Dung Doan
@kawasaki-net.ne.jp
Innovation Center of Nanomedicine (ICONM)
Innovation Center of Nanomedicine (ICONM)
Scopus Publications
Scholar Citations
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Scopus Publications
Thi Kim Dung Doan, Masakazu Umezawa, Kyohei Okubo, Masao Kamimura, and Kohei Soga
Wiley
AbstractMicelles have been extensively used in biomedicine as potential carriers of hydrophobic fluorescent dyes. Their small diameters can potentially enable them to evade recognition by the reticuloendothelial system, resulting in prolonged circulation. Nevertheless, their lack of stability in physiological environments limits the imaging utility of micelles. In particular, when a dye sensitive to water, such as IR‐1061, is encapsulated in the micelle core, the destabilized structure leads to interactions between water and dye, degrading the fluorescence. In this study, we investigated a method to improve micelle stability utilizing the electrical effect of gadolinium (Gd3+) and tetraazacyclododecane tetraacetic acid (DOTA), introduced into the micelles. Three micellar structures, one containing a poly(lactic‐co‐glycolic acid)‐block‐poly(ethylene glycol) (PLGA‐b‐PEG) block copolymer, and two other structures, including PLGA‐b‐PEG with DOTA or Gd‐DOTA introduced at the boundary of PLGA and PEG, were prepared with IR‐1061 in the core. Structures that contained DOTA at the border of the PLGA core and PEG shell exhibited much higher fluorescence intensity than probes without DOTA. With Gd3+ ions at the DOTA center, fluorescence stability was enhanced remarkably in physiological environments. Most interesting is the finding that fluorescence is enhanced with increased Gd‐DOTA concentrations. In conclusion, we found that overall fluorescence and stability are improved by introducing Gd‐DOTA at the boundary of the PLGA core and PEG shell. Improving micelle stability is crucial for further biomedical applications of micellar probes such as bimodal fluorescence and magnetic resonance imaging.
Masakazu Umezawa, Yuichi Ueya, Kotoe Ichihashi, Doan Thi Kim Dung, and Kohei Soga
Springer Science and Business Media LLC
AbstractPolymeric nanoparticles with a hydrophobic core are valuable biomedical materials with potential applications in in vivo imaging and drug delivery. These materials are effective at protecting vulnerable molecules, enabling them to serve their functions in hydrophilic physiological environments; however, strategies that allow the chemical composition and molecular weight of polymers to be tuned, forming nanoparticles to control the functional molecules, are lacking. In this article, we review strategies for designing core–shell nanoparticles that enable the effective and stable encapsulation of functional molecules for biomedical applications. IR-1061, which changes its optical properties in response to the microenvironment are useful for in vitro screening of the in vivo stability of polymeric nanoparticles. An in vitro screening test can be performed by dispersing IR-1061-encapsulated polymer nanoparticles in water, saline, buffer solution, aqueous protein solution, etc., and measuring the absorption spectral changes. Through the screening, the effects of the polarity, molecular weight, and the chiral structure of polymers consisting of polymer nanoparticles on their stability have been revealed. Based on the findings presented here, more methodologies for the effective application of various biomolecules and macromolecules with complex high-dimensional structures are expected to be developed.
Thi Kim Dung Doan, Masakazu Umezawa, Kazuno Ikeda, Kazunobu Ohnuki, Mizuki Akatsuka, Kyohei Okubo, Masao Kamimura, Masayuki Yamaguchi, Hirofumi Fujii, and Kohei Soga
American Chemical Society (ACS)
We developed a small MRI/NIR-II probe to target HER2 (tetanucleotide) breast cancer cells. The probe is composed of PLGA-b-PEG micelles encapsulated NIR-II, and Gd-DOTA is conjugated at the border of PLGA/PEG. Herceptin was then conjugated to carboxyl residues of PLGA-b-PEG chains. We examined the influence of carboxyl group ratios on the probe property stability and Herceptin concentration and the binding affinity to HER2(+) cells corresponding to the -COOH ratios. The binding assays demonstrated that the optimal surface ratio of -COOH is 5%, which is less affected by fluorescence reduction and which exhibited the highest antigen-capturing activity.
Doan Thi Kim Dung, M. Umezawa, K. Ohnuki, K. Nigoghossian, K. Okubo, Masao Kamimura, M. Yamaguchi, Hirofumi Fujii and K. Soga
Multimodal imaging can provide multidimensional information for understanding concealed microstructures or bioprocesses in biological objects. The combination of over-1000 nm near-infrared (OTN-NIR) fluorescence imaging and magnetic resonance (MR) imaging is promising in providing high sensitivity and structural information of lesions. This combination can be facilitated by the development of an imaging probe. The OTN-NIR and MR bimodal fluorescence probes reported to date primarily involve ceramic particles for fluorescence and MRI contrast enhancement effect. In this study, we designed a new bimodal OTN-NIR/MR imaging probe from organic components including an OTN-NIR fluorescent organic dye (IR-1061) encapsulated in the core of a micelle composed of poly(lactic-co-glycolic acid)-block-poly(ethylene glycol) copolymer (PLGA-PEG). For the MRI contrast, gadobutrol (Gd-DOTA) was introduced at the end of the PEG chain at various ratios. Thereafter, the OTN-NIR fluorescence and MR bimodal imaging probes of ca. 20 nm in size were successfully prepared and applied in mouse imaging. The probe exhibited absorption and emission in the OTN-NIR, and T1 contrast enhancement effects on MRI. Moreover, it demonstrated bright OTN-NIR fluorescence and MRI contrast enhancement to depict veins and observe the organs in live mice. The imaging results revealed that the Gd-DOTA introduction ratio is of great importance for controlling the biological response of the probe without reducing the contrast enhancement effect.
Thi Kim Dung Doan, Masakazu Umezawa, Hisanori Kobayashi, Atsushi Oshima, Kazuno Ikeda, Kyohei Okubo, Masao Kamimura, and Kohei Soga
The Chemical Society of Japan
Thi Kim Dung Doan, Masakazu Umezawa, Kyohei Okubo, Masao Kamimura, Masayuki Yamaguchi, Hirofumi Fujii, and Kohei Soga
Royal Society of Chemistry (RSC)
The influence of Gd-DOTA locations on the fate of imaging probe in vivo.
Bui Thi Phuong Thuy, Tran Thi Ai My, Nguyen Thi Thanh Hai, Huynh Thi Phuong Loan, Le Trung Hieu, Tran Thai Hoa, Thanh Q. Bui, Ho Nhat Tuong, Nguyen Thi Thu Thuy, Doan Kim Dung,et al.
Springer Science and Business Media LLC
K. Nigoghossian, Tsumugi Miyashita, Asuto Omura, Gil Yeroslavsky, Doan Thi Kim Dung, K. Okubo, M. Umezawa, Masao Kamimura and K. Soga
Upconverting erbium(III) complexes in N,N-dimethylformamide (DMF) were prepared via chloride ligand replacement by tetrafluoroborate, as suggested by changes in the spectral profile. Cl− removal as precipitated salts was evidenced by X-ray diffraction (XRD) analysis. The systematic spectroscopic work indicated optimal condition for complex preparation. Ions in the coordination site were controlled by adjusting the water phase, thus the amount of removed chloride salts. Maximum emission intensity, lower red-to-green ratio and narrower emission lines were achieved at molar ratios Er3+:BF4− = 1:7 and H2O:DMF = 0.23. Studies extended to downshifted luminescence of Eu3+-complex provided more evidences of effective BF4− coordination, through dependence of relative intensities between 5D0 electric dipole and magnetic dipole (5D0→7F1) transitions. Infrared spectra suggest BF4− coordination to RE.
Gil Yeroslavsky, Masakazu Umezawa, Kyohei Okubo, Karina Nigoghossian, Doan Thi Kim Dung, Keiji Miyata, Masao Kamimura, and Kohei Soga
Royal Society of Chemistry (RSC)
Encapsulation of ICG and IR-1061 in PCL–PEG micelles producing agents with increased stability of ICG and tunable PTT and PDT activity. The micelles are also useful for NIR imaging and NIR nanothermometry.
Thi Kim Dung Doan
Springer Singapore
Doan Thi Kim Dung, Masakazu Umezawa, Karina Nigoghossian, Gil Yeroslavsky, Kyohei Okubo, Masao Kamimura, Masayuki Yamaguchi, Hirofumi Fujii, and Kohei Soga
Technical Association of Photopolymers, Japan
Imaging utilizing the near-infrared (NIR) light has attracted numerous attention due to the possibility in the deep tissue penetration as it can overcome the light scattering and absorption of tissue components. The ultraviolet (UV) unlikely penetrates the skin, while the visible (VIS) light can be scattered or absorbed by tissue components. This penetration likely improves as the wavelength shifts beyond 1000 nm region (also called NIR-II). Fat tissues are ascribed to the scattering of UV or VIS, while others such as water, melanin, hemoglobin are greatly attributed to absorbing light. Using NIR over 1000 nm (OTN-NIR) is currently considered as a critical approach for real-time dynamical visualization of the structure and functional features of tissues anatomically with refrained effects of fatty scattering and water absorption. However, the attempts to image anatomical structure by OTN-NIR is laborious and time-consuming. Then, for facile human applying, magnetic resonance imaging (MRI) is used as a guiding technique to localize the sites of interest. MRI is considered the most beneficial imaging technique without ionizing radiation which provides images with high resolution, preeminent tissue contrast. MRI also can visualize a large volume such as the human body to the few millimeter objects with great signal-to-noise ratio as well as contrast-to-noise ratio. This review highlights the design of imaging probe for multimodal NIR/MR imaging, including the potential applications.
Gil Yeroslavsky, Kyohei Okubo, Masakazu Umezawa, Karina Nigoghossian, Doan Thi Kim Dung, Keiji Miyata, Koki Nomura, Masao Kamimura, and Kohei Soga
Technical Association of Photopolymers, Japan
1 Imaging Frontier Center (IFC), Research Institute for Science and Technology (RIST), Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan 2 Department of Materials Science and Technology, Tokyo University of Science, 6-3-1 Niijuku, Katsushika-ku, Tokyo 125-8585, Japan 3 Research Institute for Biomedical Science, Tokyo University of Science, 2669 Yamazaki, Noda, Chiba 278-0022, Japan 4 Division of Functional Imaging, Exploratory Oncology Research & Clinical Trial Center, National Cancer Center, 6-5-1 Kashiwanoha, Kashiwa 277-8577, Japan * kyohei.okubo@rs.tus.ac.jp
Gil Yeroslavsky, M. Umezawa, K. Okubo, K. Nigoghossian, D. K. Dung, Masao Kamimura and K. Soga
Indocyanine Green (ICG) is one of the most common fluorescent dyes that emits in the near-infrared (NIR) region, with extensive use in the medical field. However, this dye is susceptible to photobleaching, thermal degradation and oxidation in acidic conditions. The major pathway by which ICG photobleaches involves sensitization to form singlet oxygen, which can react with the dye’s backbone, resulting in decomposition to non-fluorescent debris. In this paper we introduce the concept of using energy transfer (ET) for the protection of NIR dyes against photodecomposition. The dye IR-1061 was chosen as an ET pair due to its spectral overlap with ICG. First, it was shown that the presence of the former in solution reduced disintegration of the latter by absorbance and fluorescence spectroscopy. A singlet oxygen-reactive fluorescent indicator was employed to demonstrate that the production of this reactive species is also greatly reduced. This photoprotective effect was improved by encapsulation of the dyes in phospholipid-PEG micelles, which reduces the distance between them, thus enhancing the ET efficiency. The micelles were characterized for their optical properties and their size was determined to be about 10 nm with dynamic light scattering (DLS) techniques. The ET particles displayed greater fluorescence over 1000 nm compared to either dye encapsulated alone. The micelles proved to be superior than the free dye in terms of chemical, thermal and photo-stability. Moreover, the system demonstrated improved heating due to a greater photothermal effect compared to ICG dye in free or encapsulated form.
Doan Thi Kim Dung, Shoichiro Fukushima, Taichi Furukawa, Hirohiko Niioka, Takumi Sannomiya, Kaori Kobayashi, Hiroshi Yukawa, Yoshinobu Baba, Mamoru Hashimoto, and Jun Miyake
MDPI AG
Comprehensive imaging of a biological individual can be achieved by utilizing the variation in spatial resolution, the scale of cathodoluminescence (CL), and near-infrared (NIR), as favored by imaging probe Gd2O3 co-doped lanthanide nanophosphors (NPPs). A series of Gd2O3:Ln3+/Yb3+ (Ln3+: Tm3+, Ho3+, Er3+) NPPs with multispectral emission are prepared by the sol-gel method. The NPPs show a wide range of emissions spanning from the visible to the NIR region under 980 nm excitation. The dependence of the upconverting (UC)/downconverting (DC) emission intensity on the dopant ratio is investigated. The optimum ratios of dopants obtained for emissions in the NIR regions at 810 nm, 1200 nm, and 1530 nm are applied to produce nanoparticles by the homogeneous precipitation (HP) method. The nanoparticles produced from the HP method are used to investigate the dual NIR and CL imaging modalities. The results indicate the possibility of using Gd2O3 co-doped Ln3+/Yb3+ (Ln3+: Tm3+, Ho3+, Er3+) in correlation with NIR and CL imaging. The use of Gd2O3 promises an extension of the object dimension to the whole-body level by employing magnetic resonance imaging (MRI).
Hirohiko Niioka, Jumpei Yamasaki, Doan Thi Kim Dung, and Jun Miyake
The Chemical Society of Japan
Bioimaging probes, which can emit near-infrared (NIR) light and are excitable with NIR light, are promising for deep tissue imaging in vivo. Lanthanide-doped phosphors, such as Y2O3:Tm,Yb; Y2O3:Ho,Yb; and Y2O3:Er,Yb, are candidates for the probes. We enhanced the NIR emission of the three kinds of lanthanide-doped phosphor by using Li-ion doping. The probes were applied to cellular imaging.
Doan Thi Kim Dung, Tran Hoang Hai, Le Hong Phuc, Bui Duc Long, Le Khanh Vinh and Phan Nha Truc
Magnetic chitosan nanoparticles were prepared by the suspension cross-linking technique for use in the application of magnetic carrier technology. The Fe3O4 magnetic nanoparticles were synthesized by co-precipitation of FeCl2 and FeCl3 solution in base medium for using in the preparation of the magnetic chitosan. The morphological and magnetic properties of the magnetic nanoparticles were characterized by different techniques (TEM, XRD, VSM, FTIR, etc.). The magnetic properties of chitosan – magnetic nanoparticles were analyzed by VSM, and MS around 15 emu/g.
Tran Hoang Hai, Le Hong Phuc, Doan Thi Kim Dung, Nguyen Thi Le Huyen, Bui Duc Long, Le Khanh Vinh, Nguyen Thi Thanh Kieu, and Massanori Abe
Korean Physical Society
Magnetic resonance imaging (MRI) has become a major and promising topic in medical researching because of its numerous potential applications. Due to the speci c uptake by macrophage and not entirely captured by liver and spleen at rst-pass, Superparamagnetic nanoparticles (SPIONs) are widely investigated as diagnostic tracer for magnetic resonance imaging (MRI). Surfactantcoated Fe3O4 particles (6 nm diameter) have been synthesized by using a wet chemical method (co-precipitation). Our study concentrated on synthesizing magnetic nanoparticles Fe3O4 coating oleic acid and Dextran and Starch polysaccharides.