Intranasal Delivery of Near-infrared and Magnetic Dual-response Nanospheres to Rapidly Produce Antidepressant-like and Cognitive Enhancement Effects.

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 non-addictive 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 1 ), type 2 (D 2 ) receptors and brain-derived neurotrophic factor (BDNF) to achieve a therapeutic effect. In vivo experiments demonstrated 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 was even working in non-iron deficiency (normal fed) mice, making it a promising candidate for application in enhancing learning ability. This article is protected by copyright. All rights reserved.