Multi-target And Multi-channel Treatment Of Alzheimer's Disease With Composite Nano-selenium

Alzheimer's disease?AD?is a neurodegenerative disease in which the body's neurons and structures gradually deteriorate.The patient's development from mild memory loss and cognitive impairment to severe loss of memory and involuntary behavior in the later period has seriously affected the quality of life of the individual and brought great spiritual and economic pressure to the family and society.The pathogenesis of AD is complex,including a series of associations of beta amyloid deposition,Tau protein hyperphosphorylation and oxidative stress,accompanied by other events such as neuronal loss,mitochondrial dysfunction,and neuroinflammation.Therefore,no solution has been found to cure AD or change its course of disease.This article first introduces a step-by-step release delivery system for mesoporous nano-selenium construction,which achieves multi-target synergistic treatment and effectively improves the learning and memory ability of AD mice.The drug through the blood-brain barrier?BBB???is the key to the treatment of AD.On this basis,a new material is designed and synthesized: Selenium Quantum Dots?SeQDs?,which can improve the BBB transmittance by using its small size effect,and it can delay and alleviate the disease and nerve damage of AD model mice,and play a neuroprotective role.This article is divided into the following three chapters:Chapter 1: First,the symptoms and pathological features of AD are briefly described,and the main pathological mechanisms of AD include the amyloid cascade hypothesis,the inflammatory hypothesis and the Tau protein hyperphosphorylation hypothesis.Then focus on the impact of blood-brain barrier permeability on drugs,existing strategies for the treatment of AD and the prospects of nano-drug treatment of AD.Finally,the significance and purpose of the topic of this study are explained.Chapter 2: The complex pathology of multiple causes severely limits the development of AD drugs.Controlled release,target ability,and multi-channel synergistic treatment are key factors associated with the success of AD drugs.Herein,we report a novel mesoporous nano-selenium?MSe?release delivery system?MSe-Res/Fc-?-CD/Bor?based on the borneol?Bor?target,?-cyclodextrin nanovalves?Fc-?-CD?with loaded resveratrol?Res?.Previous experiments have shown that MSe-Res/Fc-?-CD/Bor first releases Bor by interacting with blood or intracellular esterases,allowing the nanosystem to pass through the blood-brain barrier?BBB?.Subsequently,the Fc-?-CD is opened by the redox?H₂O₂?response to the release of Res at the lesion site.We demonstrated that MSe-Res/Fc-?-CD/Bor inhibited aggregation of ?-amyloid proteins?A??,mitigated oxidative stress,and suppressed tau hyperphosphorylation,while protecting nerve cells and successfully improving memory impairment in APP/PS1 mice.Interestingly,compared with rivastigmine?Riv?positive drugs alone,the MSe/Fc-?-CD/Bor loaded with Riv had a better pharmacokinetic index.These results indicate that MSe-Res/Fc-?-CD/Bor could be a prospective drug for treating AD.Chapter 3: The blood-brain barrier prevents most drugs from entering the brain,so safe and effective crossing of the blood-brain barrier is the basis for the treatment of AD.Studies have shown that quantum dots are a promising new nanomedicine material due to their small size,good solubility,large specific surface area and low cost.Based on the background of the appeal,we designed and synthesized quantum dot selenium?SeQDs?,which can quickly pass through the blood-brain barrier,help cells clear A? aggregates,and protect cells from A?-induced cytotoxic damage.Studies have shown that quantum dot selenium not only shows good degradation ability for the already formed A? fiber,but also effectively inhibits A? aggregation,prevents inflammation and maintains intracellular reactive oxygen species.In addition,through the construction of two animal models,it is further proved that quantum dot selenium can prevent the production of A? aggregates and neuronal damage in the brain of modeled AD mice,and can significantly improve the cognitive level of diseased AD mice,so quantum Selenium may be a potential drug for the prevention and treatment of AD.