Li Chan, Zhou Sheng, Chen Chuncheng, Zhu Lijun, Li Shijie, Song Zhuoyue, Liang Jian, Tang Chunzhi, Xu Nenggui, Liu Tao, Liu Shihui
Medical College of Acu-Moxi and Rehabilitation, Guangzhou University of Chinese Medicine, Guangzhou 510006, PR China.
Medical College of Acu-Moxi and Rehabilitation, Guangzhou University of Chinese Medicine, Guangzhou 510006, PR China.
Colloids Surf B Biointerfaces. 2023 May;225:113253. doi: 10.1016/j.colsurfb.2023.113253. Epub 2023 Mar 7.
Disulfiram (DSF), a drug for alcohol withdrawal, has attracted extensive scientific attention due to its potential to treat cancer. The metabolite of DSF, diethyl dithiocarbamate (DDTC), forms a Cu-DDTC complex in vivo with copper ions, which has been shown to be a proteasome inhibitor with high antitumor activity. However, the in vivo stability of Cu-DDTC complexes remains a challenge. In this study, the nanomedicine Cu-BTC@DDTC with high antitumor activity was prepared by using the nanoscale metal-organic framework (MOF) Cu-BTC as a carrier and loading diethyldithiocarbamate (DDTC) through coordination interaction. The results showed that Cu-BTC@DDTC had high drug loading and adequate stability, and exhibited DDTC-Cu(I) chemical valence characteristics and polycrystalline structure features. In vitro cytocompatibility investigation and animal xenograft tumor model evaluation demonstrated the anti-cancer potential of Cu-BTC@DDTC, especially the combination of Cu-BTC@DDTC with low-dose cisplatin showed significant antitumor effect and biosafety. This study provides a feasible protocol for developing antitumor drugs based on the drug repurposing strategy.
双硫仑（DSF）是一种用于戒酒的药物，因其治疗癌症的潜力而受到广泛的科学关注。DSF的代谢产物二乙基二硫代氨基甲酸盐（DDTC）在体内与铜离子形成Cu-DDTC复合物，该复合物已被证明是一种具有高抗肿瘤活性的蛋白酶体抑制剂。然而，Cu-DDTC复合物在体内的稳定性仍然是一个挑战。在本研究中，以纳米级金属有机框架（MOF）Cu-BTC为载体，通过配位相互作用负载二乙基二硫代氨基甲酸盐（DDTC），制备了具有高抗肿瘤活性的纳米药物Cu-BTC@DDTC。结果表明，Cu-BTC@DDTC具有较高的载药量和足够的稳定性，并表现出DDTC-Cu（I）的化学价特征和多晶结构特征。体外细胞相容性研究和动物异种移植肿瘤模型评估证明了Cu-BTC@DDTC的抗癌潜力，特别是Cu-BTC@DDTC与低剂量顺铂联合使用显示出显著的抗肿瘤效果和生物安全性。本研究为基于药物再利用策略开发抗肿瘤药物提供了一种可行的方案。
