Using Levothyroxin‐Loaded Zn‐Curcumin MOF to Achieve Collaborative Treatment of Hypothyroidic Encephalopathy through Reducing Oxidative Stress and Re‐Building Synaptic Plasticity

Abstract Hypothyroid encephalopathy refers to cognitive impairment caused by hypothyroidism, which is caused by low thyroid hormone signal in the brain, and further leads to an increase in oxidative stress level, a decrease in hippocampal synaptic plasticity, and even affects the signal transmission process between neurons. However, traditional hormone replacement therapy (HRT) only restores the thyroid hormone concentration in serum, not in the brain, which leads to damage to hippocampal synaptic plasticity in the brain that can't be repaired. In addition, there is also oxidative damage, which makes the symptoms of encephalopathy still persist, and indicates the need for a new collaborative treatment approach for hypothyroid encephalopathy disease. In this study, a synergistic therapy system is constructed using Zn‐Curcumin‐based metal–organic framework (medi‐MOF‐1) with levothyroxine‐4 is loaded (LT4@medi‐MOF‐1). The results showed that LT4@medi‐MOF‐1 can efficiently deliver thyroid hormone into the brain, co‐release hormones and curcumin, and restore thyroid hormone levels in the brain. Furthermore, the curcumin can repair oxidative damage, and hormones and curcumin can work together to enhance synaptic plasticity. In the hypothyroidism rat model, LT4@medi‐MOF‐1 exhibits excellent capacity in ameliorating spatial learning and memory deficits, and shows the potential of a hypothyroid encephalopathy agent for cooperative treatment.