• Title/Summary/Keyword: pH-gradient

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Development of High Intensity Focused Ultrasound (HIFU) Mediated AuNP-liposomal Nanomedicine and Evaluation with PET Imaging

  • Ji Yoon Kim;Un Chul Shin;Ji Yong Park;Ran Ji Yoo;Soeku Bae;Tae Hyeon Choi;Kyuwan Kim;Young Chan Ann;Jin Sil Kim;Yu Jin Shin;Hokyu Lee;Yong Jin Lee;Kyo Chul Lee;Suhng Wook Kim;Yun-Sang Lee
    • Journal of Radiopharmaceuticals and Molecular Probes
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    • v.9 no.1
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    • pp.9-16
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    • 2023
  • Liposomes as drug delivery system have proved useful carrier for various disease, including cancer. In addition, perfluorocarbon cored microbubbles are utilized in conjunction with high-intensity focused-ultrasound (HIFU) to enable simultaneous diagnosis and treatment. However, microbubbles generally exhibit lower drug loading efficiency, so the need for the development of a novel liposome-based drug delivery material that can efficiently load and deliver drugs to targeted areas via HIFU. This study aims to develop a liposome-based drug delivery material by introducing a substance that can burst liposomes using ultrasound energy and confirm the ability to target tumors using PET imaging. Liposomes (Lipo-DOX, Lipo-DOX-Au, Lipo-DOX-Au-RGD) were synthesized with gold nanoparticles using an avidin-biotin bond, and doxorubicin was mounted inside by pH gradient method. The size distribution was measured by DLS, and encapsulation efficiency of doxorubicin was analyzed by UV-vis spectrometer. The target specificity and cytotoxicity of liposomes were assessed in vitro by glioblastoma U87mg cells to HIFU treatment and analyzed using CCK-8 assay, and fluorescence microscopy at 6-hour intervals for up to 24 hours. For the in vivo study, U87mg model mouse were injected intravenously with 1.48 MBq of 64Cu-labeled Lipo-DOX-Au and Lipo-DOX-Au-RGD, and PET images were taken at 0, 2, 4, 8, and 24 hours. As a result, the size of liposomes was 108.3 ± 5.0 nm at Lipo-DOX-Au and 94.1 ± 12.2 nm at Lipo-DOX-Au-RGD, and it was observed that doxorubicin was mounted inside the liposome up to 52%. After 6 hours of HIFU treatment, the viability of U87mg cells treated with Lipo-DOX-Au decreased by around 20% compared to Lipo-DOX, and Lipo-DOX-Au-RGD had a higher uptake rate than Lipo-DOX. In vivo study using PET images, it was confirmed that 64Cu-Lipo-DOX-Au-RGD was taken up into the tumor immediately after injection and maintained for up to 4 hours. In this study, drugs released from liposomes-gold nanoparticles via ultrasound and RGD targeting were confirmed by non-invasive imaging. In cell-level experiments, HIFU treatment of gold nanoparticle-coupled liposomes significantly decreased tumor survival, while RGD-liposomes exhibited high tumor targeting and rapid release in vivo imaging. It is expected that the combination of these models with ultrasound is served as an effective drug delivery material with therapeutic outcomes.

Limno-Biological Investigation of Lake Ok-Jeong (옥정호의 육수생물학적 연구)

  • SONG Hyung-Ho
    • Korean Journal of Fisheries and Aquatic Sciences
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    • v.15 no.1
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    • pp.1-25
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    • 1982
  • Limnological study on the physico-chemical properties and biological characteristics of the Lake Ok-Jeong was made from May 1980 to August 1981. For the planktonic organisms in the lake, species composition, seasonal change and diurnal vertical distribution based on the monthly plankton samples were investigated in conjunction with the physico-chemical properties of the body of water in the lake. Analysis of temperature revealed that there were three distinctive periods in terms of vertical mixing of the water column. During the winter season (November-March) the vertical column was completely mixed, and no temperature gradient was observed. In February temperature of the whole column from the surface to the bottom was $3.5^{\circ}C$, which was the minimum value. With seasonal warming in spring, surface water forms thermoclines at the depth of 0-10 m from April to June. In summer (July-October) the surface mixing layer was deepened to form a strong thermocline at the depth of 15-25 m. At this time surface water reached up to $28.2^{\circ}C$ in August, accompanied by a significant increase in the temperature of bottom layer. Maximum bottom temperature was $r5^{\circ}C$ which occurred in September, thus showing that this lake keeps a significant turbulence Aehgh the hypolimnial layer. As autumn cooling proceeded summer stratification was destroyed from the end of October resulting in vertical mixing. In surface layer seasonal changes of pH were within the range from 6.8 in January to 9.0 in guutuost. Thighest value observed in August was mainly due to the photosynthetic activity of the phytoplankton. In the surface layer DO was always saturated throughout the year. Particularly in winter (January-April) the surface water was oversaturated (Max. 15.2 ppm in March). Vertical variation of DO was not remarkable, and bottom water was fairly well oxygenated. Transparency was closely related to the phytoplankton bloom. The highest value (4.6 m) was recorded in February when the primary production was low. During summer transparency decreased hand the lowest value (0.9 m) was recorded in August. It is mainly due to the dense blooming of gnabaena spiroides var. crassa in the surface layer. A. The amount of inorganic matters (Ca, Mg, Fe) reveals that Lake Ok-Jeong is classified as a soft-water lake. The amount of Cl, $NO_3-N$ and COD in 1981 was slightly higher than those in 1980. Heavy metals (Zn, Cu, Pb, Cd and Hg) were not detectable throughout the study period. During the study period 107 species of planktonic organisms representing 72 genera were identified. They include 12 species of Cyanophyta, 19 species of Bacillariophyta, 23 species of Chlorophyta, 14 species of Protozoa, 29 species of Rotifera, 4 species of Cladocera and 6 species of Copepoda. Bimodal blooming of phytoplankton was observed. A large blooming ($1,504\times10^3\;cells/l$ in October) was observed from July to October; a small blooming was present ($236\times10^3\;cells/l$ in February) from January to April. The dominant phytoplankton species include Melosira granulata, Anabaena spiroides, Asterionella gracillima and Microcystis aeruginota, which were classified into three seasonal groups : summer group, winter group and the whole year group. The sumner group includes Melosira granulate and Anabaena spiroides ; the winter group includes Asterionella gracillima and Synedra acus, S. ulna: the whole year group includes Microtystis aeruginosa and Ankistrodesmus falcatus. It is noted that M. granulate tends to aggregate in the bottom layer from January to August. The dominant zooplankters were Thermocpclops taihokuensis, Difflugia corona, Bosmina longirostris, Bosminopsis deitersi, Keratelle quadrata and Asplanchna priodonta. A single peak of zooplankton growth was observed and maximum zooplankton occurrence was present in July. Diurnal vertical migration was revealed by Microcystis aeruginosa, M. incerta, Anabaena spiroides, Melosira granulata, and Bosmina longirostris. Of these, M. granulata descends to the bottom and forms aggregation after sunset. B. longirostris shows fairly typical nocturnal migration. They ascends to the surface after sunset and disperse in the whole water column during night. Foully one species of fish representing 31 genera were collected. Of these 13 species including Pseudoperilnmpus uyekii and Coreoleuciscus splendidus were indigenous species of Korean inland waters. The indicator species of water quality determination include Microcystis aeruginosa, Melosira granulata, Asterionelta gracillima, Brachionus calyciflorus, Filinia longiseta, Conochiloides natans, Asplanchna priodonta, Difflugia corona, Eudorina elegans, Ceratium hirundinella, Bosmina longirostris, Bosminopsis deitersi, Heliodiaptomus kikuchii and Thermocyclops taihokuensis. These species have been known the indicator groups which are commonly found in the eutrophic lakes. Based on these planktonic indicators Lake Ok-Jeong can be classified into an eutrophic lake.

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