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基于纳米医学的双硫仑与金属离子共递送癌症治疗策略

Nanomedicine-based disulfiram and metal ion co-delivery strategies for cancer treatment.

作者信息

Shen Xinyue, Sheng Huixiang, Zhang Ying, Dong Xuan, Kou Longfa, Yao Qing, Zhao Xinyu

机构信息

The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China.

School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, China.

出版信息

Int J Pharm X. 2024 Apr 18;7:100248. doi: 10.1016/j.ijpx.2024.100248. eCollection 2024 Jun.

Abstract

Disulfiram (DSF) is a second-line drug for the clinical treatment of alcoholism and has long been proven to be safe for use in clinical practice. In recent years, researchers have discovered the cancer-killing activity of DSF, which is highly dependent on the presence of metal ions, particularly copper ions. Additionally, free DSF is highly unstable and easily degraded within few minutes in blood circulation. Therefore, an ideal DSF formulation should facilitate the co-delivery of metal ions and safeguard the DSF throughout its biological journey before reaching the targeted site. Extensive research have proved that nanotechnology based formulations can effectively realize this goal by strategic encapsulation therapeutic agents within nanoparticle. To be more specific, this is accomplished through precise delivery, coordinated release of metal ions at the tumor site, thereby amplifying its cytotoxic potential. Beyond traditional co-loading techniques, innovative approaches such as DSF-metal complex and metal nanomaterials, have also demonstrated promising results at the animal model stage. This review aims to elucidate the anticancer mechanism associated with DSF and its reliance on metal ions, as well as to provide a comprehensive overview of recent advances in the arena of nanomedicine based co-delivery strategies for DSF and metal ion in the context of cancer therapy.

摘要

双硫仑(DSF)是用于酒精中毒临床治疗的二线药物,长期以来已被证明在临床实践中使用是安全的。近年来,研究人员发现了DSF的抗癌活性,其高度依赖于金属离子尤其是铜离子的存在。此外,游离的DSF非常不稳定,在血液循环中几分钟内就容易降解。因此,理想的DSF制剂应有助于金属离子的共同递送,并在其到达靶位点之前的整个生物学过程中保护DSF。大量研究证明,基于纳米技术的制剂可以通过将治疗剂战略性地封装在纳米颗粒中来有效实现这一目标。更具体地说,这是通过精确递送、在肿瘤部位协调释放金属离子来实现的,从而增强其细胞毒性潜力。除了传统的共载技术外,诸如DSF-金属络合物和金属纳米材料等创新方法在动物模型阶段也已显示出有前景的结果。本综述旨在阐明与DSF相关的抗癌机制及其对金属离子的依赖性,并全面概述在癌症治疗背景下基于纳米医学的DSF和金属离子共同递送策略领域的最新进展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec81/11059435/aae5a448c5ca/ga1.jpg

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