Mesoporous Silica Nanoparticles: Preparation And Functionalization In Biomedicine

Since the discovery of MCM-41, mesoporous materials have received particularattention in many areas, such as catalysis, adsorption, separation, chemcial sensors,bioscience and so on. Mesoporous silica nanomaterials (MSNs) have more potentialfor above applications because of their nano-scaled size, in particular for a variety ofnanotechnological applications including biomedicine and biotechnology. Comparedwith that of MSNs, Hollow mesopourous silica nanoparticles (HMSNs) have theproperties of the lower apparent density, the broader loading of substance, and thesustained release, which lead to their extensive applications in biomedicine especiallyin drug loading and delivery. It is important to synthesize the two kinds ofnanomaiterial and further investigate their functionalization and applications inbiomedicine. Main research results during my Ph. D. study are described as follows.1. We synthesized highly ordered size-tunable MSNs and chose MSNs sampleswith particle diameters of80nm,200nm, and320nm to be used as objectinvestigated. MSNs with particle diameter of80nm were firstly synthesized andwere further modified with various amounts of3-aminopropyltriethoxysilane(APTES), respectively, by a direct co-condensation method. The amount of APTESwas varied from15:1to2:1(the molar ratio of TEOS to APTES). All the sampleswere employed to complex with plasmid DNA (pDNA) to study their adsorption andprotection capacities. The results demonstrate the MSNs functionalized withaminopropyl groups present advanced adsorption capacities for DNA immobilization.And Am-MSNs with high APTES amount lead to high amount of pDNA adsorption.Further investigation of pDNA protection shows Am-MSNs with Smaller and/orhigher amount of APTES could partially provide protection of pDNA, whileAm-MSNs with moderate APTES amount could completely protect pDNA from enzymatic degradation. That is to say Am-MSNs with moderate amount of APTESexhibit good adsorption and protection capacities for pDNA, which implies thecorresponding samples might be good candidates for gene carriers. Based on theabove result we used the sample4(7.5:1refer to the molar ratio of TEOS to APTES)to interact with other pDNA, pcDNA3.1(+)-PKB-HA and PEGFPN3. The resultsdemonstrated that sample4shows good adsorption and protection capacities forpcDNA3.1(+)-PKB-HA and PEGFPN3, which implies that the nanoparticles areversatile material for pDNA. Then we employed the sample as genecarrier forpcDNA3.1(+) and studied transfection preliminarily. The experimental results ofextremely low transfection efficiency show that it is possible for MSNs to be used asgenecarrier which is needed further investigation.2. Subsequently, we synthesized Am-MSNs-200and Am-MSNs-320withvarious amounts of APTES by a direct co-condensation method, respectively. Theresults of samples Am-MSNs-200adsorbing and protecting pcDNA3.1(+) reveal thatthe material with moderate amount of APTES not only highly adsorbed pDNA butalso provide total protection for pDNA, which is as the same as that of Am-MSNs-80.For the samples Am-MSNs-320, the amount of adsorption is directly proportional tothe amount of APTES. However, the sample Am-MSNs-320-10:1can not retard DNAmigration, indicating the particle size also affects the adsorption in despite of the mainfactor of electrostatic interaction between pDNA and Am-MSNs. Also the amount ofAPTES on Am-MSNs-320influences the protection capacity for pDNA. However,most of samples can not efficiently protect pDNA, which shows that samples withlarger particle size exhibit less advantage for pDNA adsorption and adsorption.3. Three functionalized MSNs, chitosan modified MSNs (C-F-Am-MSNs),hydroxyapatite coated MSNs (F-Am-HA-MSNs), and PEGylation MSNs(PEG-F-Am-MSNs) were synthesized by post modification and were evaluated the invitro biocompatibility and endocytosis. The results show that F-Am-HA-MSNs andPEG-F-Am-MSNs have higher biocompatibility than that of C-F-Am-MSNs. Amongthe three materials PEG-F-Am-MSNs exhibit higher cell uptake than that of others. Itindicates that the functionalized MSNs especially PEGylation MSNs have greatpractical and potential application in biomedicine.4. Owning to the great potential in drug loading and delivery, we preparedHMSNs by using CaCO3template. We focused on the monodispersed nomoparticles so that the materials are supposed to show excellent endocytosis properties, which isthe basis of drug delivery. The preliminary result shows that the HMSNsas-synthisized have good biocompatibility and polydispersity with DPI=0.2.