State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China.
School of Chemical and Material Engineering, Jiangnan University, Wuxi 214122, China.
J Mater Chem B. 2022 Mar 30;10(13):2251-2259. doi: 10.1039/d1tb02862f.
Targeted radionuclide therapy (TRT) has been a promising strategy for cancer therapy, which can inhibit or kill cancer cells by selectively delivering radionuclide to target tissues. Herein, a legumain-targeted therapeutic agent [I]MAAN was synthesized that was capable of condensation and self-assembly in response to legumain and glutathione (GSH) in tumor cells to enhance the therapeutic effect. This radiopharmaceutical has been acquired with a radiochemical yield (RCY) of 57.8 ± 5.3% and a high radiochemical purity (RCP) of more than 95%. cellular uptake assay suggested that [I]MAAN had a 2-fold higher uptake in legumain-positive HCT116 cells than in the legumain-negative SKOV3 cells, revealing the specificity of the agent for legumain. Similarly, the cytotoxicity assay showed that [I]MAAN possessed a more obvious killing effect on HCT116 cells. Cerenkov imaging with [I]MAAN was carried out to generate clear tumor images. TRT with [I]MAAN significantly inhibited the tumor growth and no obvious toxicity towards other normal organs was observed, indicating that it is a safe and effective treatment for cancers. Therefore, the agent [I]MAAN holds great potential for the diagnosis and treatment of cancers with a high expression level of legumain.
靶向放射性核素治疗（TRT）一直是癌症治疗的一种很有前途的策略，它可以通过选择性地将放射性核素递送到靶组织来抑制或杀死癌细胞。本文合成了一种组织蛋白酶靶向治疗剂[I]MAAN，它能够在肿瘤细胞中响应组织蛋白酶和谷胱甘肽（GSH）进行缩合和自组装，从而增强治疗效果。这种放射性药物的放射化学产率（RCY）为 57.8±5.3%，放射化学纯度（RCP）超过 95%。细胞摄取实验表明，[I]MAAN 在组织蛋白酶阳性的 HCT116 细胞中的摄取量是组织蛋白酶阴性的 SKOV3 细胞的 2 倍，表明该药物对组织蛋白酶具有特异性。同样，细胞毒性实验表明，[I]MAAN 对 HCT116 细胞具有更明显的杀伤作用。用[I]MAAN 进行的 Cerenkov 成像产生了清晰的肿瘤图像。用[I]MAAN 进行的 TRT 显著抑制了肿瘤生长，并且对其他正常器官没有明显的毒性，表明它是一种安全有效的癌症治疗方法。因此，该试剂[I]MAAN 具有很大的潜力用于诊断和治疗组织蛋白酶表达水平较高的癌症。
