Scientific Research Center, China-Japan Union Hospital of Jilin University, Changchun, 130033, People's Republic of China.
Jilin University School of Pharmaceutical Sciences, Changchun, 130021, People's Republic of China.
Int J Nanomedicine. 2024 Jul 24;19:7547-7566. doi: 10.2147/IJN.S471734. eCollection 2024.
Cancer poses a significant threat to human life and health. Chemotherapy is currently one of the effective cancer treatments, but many chemotherapy drugs have cell toxicity, low solubility, poor stability, a narrow therapeutic window, and unfavorable pharmacokinetic properties. To solve the above problems, target drug delivery to tumor cells, and reduce the side effects of drugs, an anti-tumor drug delivery system based on tumor microenvironment has become a focus of research in recent years. The construction of a reduction-sensitive nanomedicine delivery system based on disulfide bonds has attracted much attention. Disulfide bonds have good reductive responsiveness and can effectively target the high glutathione (GSH) levels in the tumor environment, enabling precise drug delivery. To further enhance targeting and accelerate drug release, disulfide bonds are often combined with pH-responsive nanocarriers and highly expressed ligands in tumor cells to construct drug delivery systems. Disulfide bonds can connect drug molecules and polymer molecules in the drug delivery system, as well as between different drug molecules and carrier molecules. This article summarized the drug delivery systems (DDS) that researchers have constructed in recent years based on disulfide bond drug delivery systems targeting the tumor microenvironment, disulfide bond cleavage-triggering conditions, various drug loading strategies, and carrier design. In this review, we also discuss the controlled release mechanisms and effects of these DDS and further discuss the clinical applicability of delivery systems based on disulfide bonds and the challenges faced in clinical translation.
癌症对人类的生命和健康构成了重大威胁。化疗是目前癌症治疗的有效手段之一，但许多化疗药物具有细胞毒性、低溶解度、差的稳定性、窄治疗窗和不利的药代动力学特性。为了解决上述问题，实现靶向递送到肿瘤细胞，并降低药物的副作用，基于肿瘤微环境的抗肿瘤药物传递系统已成为近年来研究的重点。基于二硫键的还原敏感型纳米药物传递系统的构建引起了广泛关注。二硫键具有良好的还原响应性，可以有效地针对肿瘤环境中高谷胱甘肽（GSH）水平，实现精确的药物传递。为了进一步增强靶向性并加速药物释放，二硫键通常与 pH 响应性纳米载体和肿瘤细胞中高表达的配体结合，构建药物传递系统。二硫键可以连接药物分子和药物传递系统中的聚合物分子，以及不同药物分子和载体分子之间。本文总结了近年来研究人员基于针对肿瘤微环境的二硫键药物传递系统、二硫键断裂触发条件、各种药物装载策略和载体设计构建的药物传递系统（DDS）。在这篇综述中，我们还讨论了这些 DDS 的控制释放机制和效果，并进一步讨论了基于二硫键的传递系统的临床适用性和临床转化所面临的挑战。
