Journal of Radiopharmaceuticals and Molecular Probes (대한방사성의약품학회지)

Korean Society of Radiopharmaceuticals and Molecular Probes (대한방사성의약품학회)
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Development of High Intensity Focused Ultrasound (HIFU) Mediated AuNP-liposomal Nanomedicine and Evaluation with PET Imaging

  • Ji Yoon Kim (Department of Nuclear Medicine, Seoul National University College of Medicine) ;
  • Un Chul Shin (School of Health and Environmental Science College of Health Science, Korea University) ;
  • Ji Yong Park (Department of Nuclear Medicine, Seoul National University College of Medicine) ;
  • Ran Ji Yoo (Department of Nuclear Medicine, Seoul National University Hospital, College of Medicine) ;
  • Soeku Bae (School of Health and Environmental Science College of Health Science, Korea University) ;
  • Tae Hyeon Choi (Department of Nuclear Medicine, Seoul National University College of Medicine) ;
  • Kyuwan Kim (Department of Nuclear Medicine, Seoul National University Hospital, College of Medicine) ;
  • Young Chan Ann (Department of Nuclear Medicine, Seoul National University Hospital, College of Medicine) ;
  • Jin Sil Kim (Department of Nuclear Medicine, Seoul National University College of Medicine) ;
  • Yu Jin Shin (Department of Nuclear Medicine, Seoul National University Hospital, College of Medicine) ;
  • Hokyu Lee (Research Professor, Medical Device Innovation Center, Korea University) ;
  • Yong Jin Lee (Division of Applied RI, Korea Institute of Radiological and Medical Sciences (KIRAMS)) ;
  • Kyo Chul Lee (Division of Applied RI, Korea Institute of Radiological and Medical Sciences (KIRAMS)) ;
  • Suhng Wook Kim (School of Health and Environmental Science College of Health Science, Korea University) ;
  • Yun-Sang Lee (Department of Nuclear Medicine, Seoul National University College of Medicine)
  • Received : 2023.06.08
  • Accepted : 2023.06.20
  • Published : 2023.06.30
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Abstract

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.

Keywords

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