Surface Modification And Functionalization Of Mesoporous Silica Nanoparticles

Due to its unique properties i.e.facile regulation on composition,structure and surface modification,large specific surface area,tunable pore size,good biocompatibility and safety,mesoporous porous silica nanoparticles?MSNs?have been widely applied to the biomedical fields,for example adsorption separation,biological catalysis,biological imaging,drug delivery and tissue engineering,etc.Though more and more attentions have focused on the targeting therapy and tissue engineering,some problems still hinder their progresses,such as a small accumulation in the tumor,large particle size,poor dispersion stability of MSNs and insufficient mechanical properties of hydrogel caused by incorporation of bare MSNs.Aiming for the problems,the following two researches were carried out:?1?Surface modification and fuctionalization of mesoporous silica nanoparticles for tumor-targeted high intensity focused ultrasound?HIFU?ablation.In this chapter,MSNs modified with carboxyl groups and Polyethylene Glycol?PEG??namely PMSNs?were obtained with size of around 60 nm,by introducing short chain silane coupling agent composed of functional PEG during the hydrolysis and condensation of silicon source.The obtained PMSNs have large specific surface areas(359 m²?g^-1)and mesoporous structure?2.2 nm?and display a good dispersion stability in the neutral phosphate buffer solution?PBS?without obvious aggregation.Furthermore,fluorescent molecular Cyanine5 amine?Cy5?and targeted molecule iRGD were modified onto the PMSNs via the carboxyl groups.The results of cell uptake and fluorescent imaging in vivo show more nanoparticles accumulation of targeting group in tumor than those of non-targeting groups.Besides,vinyl azide?VA?was loaded into PMSNs to investigate HIFU ablation for bovine liver in vitro.The results show that under different power HIFU irradiation for 10 s,the ablation volume of bovine liver for experimental group?VA@PMSNs?is around 1 and 3 times than those of the control groups?PBS and PMSNs?.The synergistic mechanism is supposed to the cavitation effect caused by nitrogen derived from decomposition of VA on the local high temperature condition.Although active targeting modification improves the enrichment of nanoparticles in tumor area and the synergistic therapeutic effect,the way of administration by vein still can not meet the requirements for the clinical safety.Thus,it is essential to further develop nanocomposite hydrogel which can realize local administrate,as follows.?2?The preparation and performance research of MSNs reinforced nanocomposite hydrogel.In this chapter,the mesoporous silica nanoparticles modified with carboxyl groups were used as crosslinking agents to incorporated into GelMA polymer to construct a novel nanocomposite hydrogel?namely MSNs-COOH@gGel?for stem cells adhesion and growth.The obtained MSNs-COOH with an average particle size of89 nm,specific surface area(434 m²?g^-1)and mesoporous structure?3.5 nm?can be used as nanocarriers for loading drug.The IR and TG results display the successful modification of carboxyl groups on the surface of MSNs.The results of mechanical test demonstrate that compression modulus of MSNs-COOH@gGel increases gradually with the increasing concentration of MSNs-COOH.Specially,when the Si concentration at 1 mg?mL^-1,compression modulus?11.1 KPa?is 3.4 times and 1.5 times than those of GelMA hydrogel?namely gGel??3.28 KPa?and MSNs@gGel?abbreviated as MSNs added to hydrogel??7.7 KPa?.The reason for the reinforcement can be ascribed to the addition of nanoparticles can effectively disperse mechanical stress in polymer network.Furthermore,the surface carboxyl groups of MSNs-COOH can strongly interact with amino and methyl acrylamide groups presented in polymer chain,making mechanical strength even more reinforced.Besides,Pinacidil,a drug promoting stem cell adhesion and growth,was loaded into MSNs-COOH to obtain drug loading and sustained release hydrogel.The results of fluorescence confocal imaging show stem cells are easy to adhere and spread on/into the hydrogel with the formation of pseudopodia and branched intercontact network structure.In short,both the reinforcement of mechanical strength and drug loading are beneficial for adhesion and growth of stem cells between the pores of hydrogel.