Construction Of Biomimetic Interface And Its Application In Alzheimer’s Disease And Tumor Therapy

With the continuous application of biomimetic technology in various fields,the development of biomimetic interfaces and their application in many fields have received extensive attention.For example,in the field of chemistry,a super-hydrophobic interface is constructed by simulating lotus leaves;in the medical field,researchers manufactured many bionic devices that can replace human organs.In the study of the pathogenesis of Alzheimer’s disease,although studies have shown that the bionic cell membrane interface constructed by phospholipids has a certain effect on the formation of amyloid fibrils,the physical factors on the surface of the cell membrane are important for the process of oligomerization transfer to the formation of amyloid fibrils which lack further research;in the study of tumor treatment,there have been many drugs and nano-loading systems that have good effects on tumor treatment.But how to effectively deliver drugs into the tumor has been a huge challenge in this field.Researchers have established a 3D tumor model to quickly screen drugs and nano drug-loading systems.However,the mechanism of 3D tumor models hindering drug penetration and how to break through the hindrance of tumor models to drugs and nano drug-loading systems remain to be resolved.In response to the above challenges,this paper starts from the biomimetic interface at the cell level and the intercellular level,and it mainly research the following two aspects: 1.To explore the mechanism of the action of amyloid oligomers in the formation of amyloid fibrils and the toxicity of amyloid fibrils to nerve cells by simulating the physical conditions on the surface of the cell membrane with negative charges.The specific work is as follows: thioflavin-T(Th T)combined test to explore the formation kinetics of amyloid;through inverted fluorescence microscopy(FM)and atomic force microscopy(AFM)to explore the egg white lysozyme(HEWL)mediated by the cell membrane bionic interface and Aβ(1-40)amyloid fibril formation process and mechanism;through the WST-1 experiment to explore the toxicity of the naturally formed amyloid protein and amyloid protein mediated by the cell membrane bionic interface to neuroblastoma cells(SH-SY5Y),respectively;To investigate the effects of amyloid fibrils mediated by the cell membrane bionic interface on dispersed neural stem cells(NSCs)and neurospheres through real-time live cell fluorescence microscopy.The results showed that the non-toxic amyloid oligomer rapidly developed into amyloid fibrils on the surface of negatively charged mica,revealing a way to form amyloid fibrils.During this process,after Aβ monomer stimulated,larger amyloid aggregates will form,which will be captured and arranged by the negatively charged surface and transformed into neurotoxic amyloid fibril structures.These fibril structures showed obvious cytotoxicity on both SH-SY5 Y and NSCs.Therefore,we propose that the interaction between chemical and physical environmental conditions should play an important role in the development of neurodegenerative diseases.2.A tumor-like model was constructed by fibroblasts(3T3)and liver cancer cells(Hep G2),and the tumor matrix biomimetic interface is the fibroblast collagen matrix(FCM)which is composed of 3T3 and collagen.Study the reasons for hindering the penetration of nanoparticles and study the methods to break through the bionic interface.The specific work is as follows: the tumor-like model is constructed by droplets,and the structure of the 3D tumor-like model is clarified by FM: 3T3 cells are mainly distributed in the outer area of the tumor-like model,and the inner area is mainly composed of Hep G2 cells;by Masson trichrome staining kit explored the mechanism of tumor-like model interstitial layer hindering particle penetration.The results showed that the collagen secreted by 3T3 cells played a supporting role in the structure of tumor-like model,and the main reason for hindering the penetration of nanoparticles is the bionic interface of tumor interstitial which composed of collagen and 3T3 cells protecting the tumor-like model which is very similar to the extracellular matrix in the tumor microenvironment;By screening between different combinations and experimental order of macrophages and magnetic nanoparticles(TPP-SPIONs)modified mitochondrial targeting molecules(triphenylphosphonium cation,TPP)and magnetic hyperthermia(MHT)to determine the experimental scheme that can break through the tumor-like model interstitial layer to kill 50% of tumor cells: After incubating TPP-SPIONs with a tumor-like model,perform the first MHT,then incubate TPP-SPIONs with RAW cells,add them to the tumor-like model after MHT,incubate for 24 hours,and finally perform the second MHT.The mechanism of protocol is: The electrostatic interaction between the positive charge on the surface of TPP-SPIONs and the negative charge on the tumor-like model causes TPP-SPIONs to adsorb on the surface of the tumor-like model and penetrate into the fibroblast collagen matrix(FCM)layer,after the MHT,the high temperature generated by TPP-SPIONs causes cracks in the FCM layer,causing TPP-SPIONs-loaded RAW cells to adsorb on the surface of the tumor-like model through electrostatic interaction and enter the FCM layer.RAW cells recruited 3T3 to consume the collagen in the protective layer,resulting in the destruction of the protective layer.Finally,the RAW cells carrying TPP-SPIONs reached the central area.After MHT again,the high temperature caused Hep G2 cells to apoptosis.The bionic interface at the cell and cell level constructed in this paper provides new methods and ideas for the design and development of new biological interfaces,as well as effective tools and experimental guidance for Alzheimer’s disease and tumor treatment research.