Institute of Biomedical Innovation, Jiangxi Medical College, School of Life Sciences, Nanchang University, Nanchang, 330088, P. R. China.
The National Engineering Research Center for Bioengineering Drugs and Technologies, Institute of Translational Medicine, Nanchang University, Nanchang, 330088, P. R. China.
Adv Mater. 2024 Aug;36(31):e2405547. doi: 10.1002/adma.202405547. Epub 2024 May 29.
Restricted by synaptic plasticity, dopamine receptor (DR) upregulation takes a long time to work. Moreover, the impact of the blood-brain barrier (BBB) on delivery efficiency restricts the development of drugs. Taking inspiration from snuff bottles, a convenient, fast-acting, and nonaddictive nasal drug delivery system has been developed to rapidly reshape the balance of synaptic transmitters. This optical and magnetic response system called CFs@DP, comprised of carbonized MIL-100 (Fe) frameworks (CFs) and domperidone (DP), which can enter the brain via nasal administration. Under dual stimulation of near-infrared (NIR) irradiation and catecholamine-induced complexation, CFs@DP disintegrates to release iron ions and DP, causing upregulation of the dopamine type 1 (D), type 2 (D) receptors, and brain-derived neurotrophic factor (BDNF) to achieve a therapeutic effect. In vivo experiments demonstrate that the DR density of mice (postnatal day 50-60) increased in the prefrontal cortex (PFC) and the hippocampus (HPC) after 10 days of therapy, resulting in antidepressant-like and cognitive enhancement effects. Interestingly, the cognitive enhancement effect of CFs@DP is even working in noniron deficiency (normal fed) mice, making it a promising candidate for application in enhancing learning ability.
受突触可塑性的限制，多巴胺受体 (DR) 的上调需要很长时间才能发挥作用。此外，血脑屏障 (BBB) 对递送效率的影响限制了药物的发展。受鼻烟壶的启发，开发了一种方便、快速作用且无成瘾性的鼻腔药物递送系统，以快速重塑突触递质的平衡。这种称为 CFs@DP 的光学和磁响应系统由碳化 MIL-100(Fe) 骨架 (CFs) 和多潘立酮 (DP) 组成，可通过鼻内给药进入大脑。在近红外 (NIR) 辐射和儿茶酚胺诱导的复合物的双重刺激下，CFs@DP 分解以释放铁离子和 DP，导致多巴胺 1 型 (D)、2 型 (D) 受体和脑源性神经营养因子 (BDNF) 的上调，从而达到治疗效果。体内实验表明，治疗 10 天后，小鼠（出生后 50-60 天）前额叶皮层 (PFC) 和海马 (HPC) 中的 DR 密度增加，产生抗抑郁样和认知增强作用。有趣的是，CFs@DP 的认知增强作用甚至在非缺铁（正常喂养）小鼠中也有效，使其成为增强学习能力的有前途的候选药物。
