State Key laboratories of Natural and mimetic drugs and Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
Nanoscale. 2020 Apr 30;12(16):9219-9230. doi: 10.1039/d0nr00810a.
Vanadium compounds are promising anti-diabetic agents, and graphene quantum dots (GQDs) are emerging as potential drug delivery systems to improve drug solubility in water and membrane transport. Using highly dispersible and water-soluble GQDs, we herein prepared a novel GQD-VO (p-dmada) complex, in which vanadium coordination compounds [VO(p-dmada)] were packed closely on one side of the GQD sheets possibly via the π-π stacking mechanism. The in vitro tests showed that GQD-VO(p-dmada) exhibited membrane permeability (Papp) as good as that of GQDs with reduced cytotoxicity. In vivo tests on type 2 diabetic mice demonstrated that GQD-VO(p-dmada) exhibited a delayed glucose lowering profile but more profound effects on insulin enhancement and β-cell protection after three-week treatment compared to VO(p-dmada) alone. In addition, GQD alone was observed for the first time to effectively lower the blood lipid levels of the db/db mice. Overall, GQD-VO(p-dmada) showed improved pharmacokinetic performance and hypoglycemic effects, and using GQD as a nanoplatform for drug delivery may provide vast opportunities for the further design of metal-based pharmaceutical agents.
钒化合物是很有前途的抗糖尿病药物，而石墨烯量子点（GQDs）作为潜在的药物传递系统，正在出现，以提高药物在水中的溶解度和膜转运。本研究使用高分散性和水溶性的 GQDs，制备了一种新型 GQD-VO（p-dmada）配合物，其中钒配位化合物[VO（p-dmada）]可能通过π-π堆积机制紧密堆积在 GQD 片的一侧。体外试验表明，GQD-VO（p-dmada）表现出与 GQDs 相当的膜透过性（Papp），同时降低了细胞毒性。在 2 型糖尿病小鼠的体内试验中，与单独使用 VO（p-dmada）相比，GQD-VO（p-dmada）在治疗 3 周后，表现出延迟降血糖作用，但对胰岛素增强和β细胞保护的效果更明显。此外，GQD 首次被观察到可有效降低 db/db 小鼠的血脂水平。总的来说，GQD-VO（p-dmada）表现出改善的药代动力学性能和降血糖作用，使用 GQD 作为药物传递的纳米平台可能为进一步设计基于金属的药物提供广阔的机会。
