Department of Pharmacy, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou 310006, China.
College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou 311400, China.
Int J Pharm. 2020 Jun 15;583:119385. doi: 10.1016/j.ijpharm.2020.119385. Epub 2020 May 4.
Arsenic trioxide (AsO), a front-line therapeutic agent against acute promyelocytic leukemia, has a broad spectrum against malignancies. Unfortunately, the clinical application of AsO in treating hematological cancers has not been transformed to solid tumors, for its dose-limited toxicity and undesirable pharmacokinetics. The ordinary AsO loaded nanodrugs (such as liposomes, polymer micelles, albumin-based nanodrugs, and silica-based nanodrugs, etc.) still could not fuel up pharmaceuticals and eradicate toxicity for low delivery efficiency caused by the instability and severe drug leakage of formulations during circulation. Recently, the approach of forming and delivering arsenic-metal complexes which will dissociate in the tumoral environment caught our mind. This is the most effective strategy to reduce drug leakage in circulation and accumulate arsenite ions in tumor sites, therefore promote the anti-tumor effect and lighten the toxicity of the drug. This review aims to explain the formation mechanism of arsenic-metal nanocomposites and summarize the constructing strategies of the arsenic-metal nanocomplexes (arsenic-nickel, arsenic-manganese, arsenic-platinum, arsenic-gadolinium, arsenic-zinc, and arsenic-iron nanobins) loaded nanodrugs for solid tumor therapy. Furthermore, the expectations and challenges of arsenic-metal complexes containing nanodrugs for cancer therapy in the future were discussed.
三氧化二砷（As2O3）是治疗急性早幼粒细胞白血病的一线治疗药物，对恶性肿瘤具有广泛的作用。然而，由于其剂量限制毒性和不理想的药代动力学，As2O3 在治疗血液系统癌症中的临床应用尚未转化为实体瘤。普通的 As2O3 负载纳米药物（如脂质体、聚合物胶束、基于白蛋白的纳米药物和基于二氧化硅的纳米药物等）仍然无法提高药物的疗效并消除由于制剂在循环过程中不稳定和严重药物泄漏导致的低递送效率所带来的毒性。最近，形成和递送至肿瘤微环境中会发生解离的砷金属配合物的方法引起了我们的注意。这是减少循环中药物泄漏并在肿瘤部位积累亚砷酸盐离子，从而提高抗肿瘤效果并减轻药物毒性的最有效策略。本文旨在解释砷金属纳米复合材料的形成机制，并总结砷金属纳米复合物（砷-镍、砷-锰、砷-铂、砷-钆、砷-锌和砷-铁纳米笼）负载纳米药物用于实体瘤治疗的构建策略。此外，还讨论了未来含砷金属纳米药物的癌症治疗的预期和挑战。
