Choi Pyeong Seok, Lee Jun Young, Chae Jung Ho, Wadas Thaddeus, Cheng Zhen, Hur Min Goo, Park Jeong Hoon
Accelerator Radioisotope Development Team, Korea Atomic Energy Research Institute, Jeongeup Si, Jeollabuk Do 56212, Republic of Korea.
Department of Radiology, Carver College of Medicine, University of Iowa, 169 Newton Road, Iowa City, Iowa 52242, United States.
ACS Appl Mater Interfaces. 2023 Jan 25;15(3):3689-3698. doi: 10.1021/acsami.2c09195. Epub 2022 Dec 27.
Cherenkov radiation (CR) derived from the decay of diagnostic and therapeutic radionuclides is currently being studied by the scientific community to determine if these emissions can be harnessed for cancer detection and therapy. While Cherenkov luminescence imaging (CLI) has been studied in the preclinical and clinical settings, Cherenkov radiation-induced cancer therapy (CRICT) is a relatively new area of research that harnesses the emitted photons to kill cancer cells through free radical generation and DNA damage. Nanoparticles seem well suited for developing a theranostic platform that would allow researchers to visualize therapy delivery and also generate the reactive oxygen species necessary to kill cancer cells. Herein, we report the preparation of an Zr-TiO-MnO nanocomposite that incorporates transferrin onto the nanoparticle surface to enhance cancer cell growth inhibition. The incorporation of the positron emission tomography (PET) radioisotope Zr (half-life: 3.3 days) allowed for the detection of the nanoparticle using PET and for the creation of Cherenkov emissions that interacted with the nanoparticle surface to generate free radicals for therapy delivery. After preparation, these systems were observed to be stable in various media and provided excellent tumor growth control after being intratumorally injected into mice bearing CT-26 tumors. These results demonstrate that a therapeutically efficient CRICT platform can be generated using commercially available and affordable materials.
科学界目前正在研究由诊断和治疗用放射性核素衰变产生的切伦科夫辐射（CR），以确定这些辐射是否可用于癌症检测和治疗。虽然切伦科夫发光成像（CLI）已在临床前和临床环境中得到研究，但切伦科夫辐射诱导癌症治疗（CRICT）是一个相对较新的研究领域，它利用发射的光子通过产生自由基和DNA损伤来杀死癌细胞。纳米颗粒似乎非常适合开发一种诊疗平台，使研究人员能够可视化治疗递送情况，并产生杀死癌细胞所需的活性氧。在此，我们报告了一种Zr-TiO-MnO纳米复合材料的制备，该材料将转铁蛋白结合到纳米颗粒表面以增强对癌细胞生长的抑制作用。正电子发射断层扫描（PET）放射性同位素Zr（半衰期：3.3天）的掺入使得能够使用PET检测纳米颗粒，并产生与纳米颗粒表面相互作用以产生用于治疗递送的自由基的切伦科夫辐射。制备后，观察到这些系统在各种介质中稳定，并且在瘤内注射到携带CT-26肿瘤的小鼠体内后提供了出色的肿瘤生长控制。这些结果表明，可以使用市售且价格合理的材料生成治疗有效的CRICT平台。
