Biocompatibility Evaluation And Drug Application Development Of Porous Silicon Nanoparticles Under Pathological Conditions

Engineered nanomaterials have unique physico-chemical properties that make them promising for biomedical applications,including tissue regeneration,drug and gene delivery and in vivo imaging of disease progression.Biocompatibility and immunogenicity of nanomaterials under pathological conditions might be dramatically changed,yet the underlying mechanism is unknown.In this thesis,we showed that under an acute liver inflammation condition,administration of porous silicon nanoparticles(PSi NPs)remitted the hepatocellular damage and inflammation activation in a surface dependent manner.Based on isobaric labelling assisted mass spectrometry,we identified the detailed compositions of protein corona complex from different PSi NPs under a diseased condition.These results suggeststhat protein corona might perturb the inflammation by capturing the pro-inflammatory proteins which are inordinately excreted under pathological condition.This signal sequestration further attenuated the NF-?B pathway activation and cytokines production from macrophages.Therefore,our study proposed a potential mechanism for elucidating the altered immunogenicity of nanomaterials under pathological condition,which might offer insights to establish harmonized standards for assessing the biosafety of biomaterials in a disease-specific or personalized manner.Based on the results of biocompatibility evaluation,we constructed nano-delivery system using UN PSi NPs as the core.MST1/2 kinase inhibitor XMU-MP-01 and gold nanoparticles were incorporated into the pores of this system.This system was designed to identify pathologically changes in the tissues and selectively deliver drugs to these sites.The loading of a therapeutic compound(XMU-MP-1)using this nano-delivery system improved the drug solubility,precise,in situ drug delivery,and the drug-functioning time.In vivo results confirmed the superior treatment effect and better compliance of this newly developed nanoformulation than free compound.This nanosystem played a crucial role in targeting the lesion area,which helps to increase the local drug concentration that is beneficial to reverse Acute liver failure(ALF).Moreover,the residence of Au NPs within the matrix further endowed our system with the capability for CT-imaging.Taken together,our results would facilitate the biomedical application of PSi NPs,which lays the theoretical foundation for the application of mesoporous silicon nanomaterials.