Department of Labeled Compounds, Hot Labs Center, Egyptian Atomic Energy Authority, Cairo, Egypt.
Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
Cancer Biother Radiopharm. 2020 Apr;35(3):167-176. doi: 10.1089/cbr.2019.2949. Epub 2020 Feb 19.
Several nanosystems are currently being utilized to enhance the targeting efficiency of several cancer chemotherapeutic agents. This study was designed to improve tumor accumulation of iodine-125 (I)-uridine incorporation into a nanocubosomal preparation. Nanocubosomes were prepared with the aid of Glycerol mono-oleate and Pluronic F127. Each prepared nanocubosomal preparation was adequately characterized by testing their particle size, polydispersity index (PDI), ζ potential (ZP), and transmission electron microscopy. The radiolabeling of uridine with I was attempted using several oxidizing agents to achieve a high radiochemical yield, and the factors affecting the reaction yield were studied in detail. A comparative biodistribution study of free I-uridine and I-uridine loaded nanocubosomes was performed in normal and tumor bearing mice. The biodistribution was evaluated by intravenous injection of the sterile test solution, and animals were anesthetized and dissected at different time intervals postinjection (p.i.). I-uridine was obtained in a high radiochemical yield (92.5% ± 0.8%). Afterward, I uridine was incorporated in a selected nanocubosome formulation, which showed nanosized cubic particles (178.6 ± 0.90 nm) with PDI (0.301 ± 0.04) and a ZP (34.35 ± 0.4). The biodistribution studies revealed that I-uridine nanocubosomes showed higher tumor localization (3.1 ± 0.4%IA/g at 2 h p.i. and a tumor/muscle ratio of 6.2) compared with the free I-uridine (2.7% ± 0.4%IA/g at 2 h p.i. and a tumor/muscle ratio of 3.3). The results of this study confirmed that I-uridine loaded nanocubosome had better efficiency in targeting the tumor site, which makes it an adequate targeting agent for tumor imaging.
几种纳米系统目前正被用于提高几种癌症化疗药物的靶向效率。本研究旨在提高碘-125（I）-尿苷掺入纳米立方体制剂的肿瘤蓄积。纳米立方体制备过程中使用甘油单油酸酯和泊洛沙姆 F127 作为辅助剂。通过测试其粒径、多分散指数（PDI）、ζ 电位（ZP）和透射电子显微镜对每种制备的纳米立方体制剂进行充分的表征。尝试使用几种氧化剂使尿苷与 I 进行放射性标记，以获得高放射化学产率，并详细研究了影响反应产率的因素。在正常荷瘤小鼠和荷瘤小鼠中进行游离 I-尿苷和负载 I-尿苷的纳米立方体制剂的比较生物分布研究。通过静脉注射无菌测试溶液进行生物分布评估，动物在注射后不同时间间隔（p.i.）麻醉和解剖。I-尿苷获得了高放射化学产率（92.5%±0.8%）。随后，将 I 尿苷掺入选定的纳米立方体制剂中，该制剂显示出纳米级立方颗粒（178.6±0.90nm），PDI（0.301±0.04）和 ZP（34.35±0.4）。生物分布研究表明，与游离 I-尿苷相比，I-尿苷纳米立方体制剂显示出更高的肿瘤定位（2h p.i.时为 3.1%±0.4%IA/g，肿瘤/肌肉比为 6.2）（2h p.i.时为 2.7%±0.4%IA/g，肿瘤/肌肉比为 3.3）。本研究结果证实，负载 I-尿苷的纳米立方体制剂对肿瘤部位具有更好的靶向效率，使其成为肿瘤成像的合适靶向剂。
