Department of Nuclear Medicine and Tracer Kinetics, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
Department of Chemistry, Graduate School of Science, Osaka University, 1-1 Machikaneyama, Toyonaka, Osaka, 560-0043, Japan.
J Nanobiotechnology. 2021 Jul 28;19(1):223. doi: 10.1186/s12951-021-00963-9.
At is a high-energy α-ray emitter with a relatively short half-life and a high cytotoxicity for cancer cells. Its dispersion can be imaged using clinical scanners, and it can be produced in cyclotrons without the use of nuclear fuel material. This study investigated the biodistribution and the antitumor effect of At-labeled gold nanoparticles (At-AuNP) administered intratumorally.
AuNP with a diameter of 5, 13, 30, or 120 nm that had been modified with poly (ethylene glycol) methyl ether (mPEG) thiol and labeled with At (At-AuNP-S-mPEG) were incubated with tumor cells, or intratumorally administered to C6 glioma or PANC-1 pancreatic cancers subcutaneously transplanted into rodent models. Systemic and intratumoral distributions of the particles in the rodents were then evaluated using scintigraphy and autoradiography, and the changes in tumor volumes were followed for about 40 days. At-AuNP-S-mPEG was cytotoxic when it was internalized by the tumor cells. After intratumoral administration, At-AuNP-S-mPEG became localized in the tumor and did not spread to systemic organs during a time period equivalent to 6 half-lives of At. Tumor growth was strongly suppressed for both C6 and PANC-1 by At-AuNP-S-mPEG. In the C6 glioma model, the strongest antitumor effect was observed in the group treated with At-AuNP-S-mPEG with a diameter of 5 nm.
The intratumoral single administration of a simple nanoparticle, At-AuNP-S-mPEG, was shown to suppress the growth of tumor tissue strongly in a particle size-dependent manner without radiation exposure to other organs caused by systemic spread of the radionuclide.
锕[225Ac]是一种高能 α 射线发射体，半衰期相对较短，对癌细胞具有高细胞毒性。其分散度可以使用临床扫描仪进行成像，并且可以在回旋加速器中产生，而无需使用核燃料材料。本研究研究了瘤内给予锕标记的金纳米粒子（At-AuNP）的体内分布和抗肿瘤作用。
用聚乙二醇甲醚（mPEG）巯基修饰并标记锕（At-AuNP-S-mPEG）的直径为 5、13、30 或 120nm 的 AuNP 与肿瘤细胞孵育，或瘤内给予皮下移植 C6 神经胶质瘤或 PANC-1 胰腺癌的啮齿动物模型。然后使用闪烁扫描和放射自显影评估颗粒在啮齿动物中的全身和肿瘤内分布，并在大约 40 天内跟踪肿瘤体积的变化。当肿瘤细胞内吞 At-AuNP-S-mPEG 时，它具有细胞毒性。瘤内给药后，At-AuNP-S-mPEG 在相当于 6 个 At 半衰期的时间内在肿瘤中定位，不会扩散到全身器官。At-AuNP-S-mPEG 强烈抑制 C6 和 PANC-1 的肿瘤生长。在 C6 神经胶质瘤模型中，用直径为 5nm 的 At-AuNP-S-mPEG 治疗的组观察到最强的抗肿瘤作用。
通过肿瘤内单次给予简单的纳米颗粒 At-AuNP-S-mPEG，以依赖于颗粒大小的方式强烈抑制肿瘤组织的生长，而不会因放射性核素的全身扩散而对其他器官造成辐射暴露。
