Ultrasmall Mesoporous Silica Nanoparticles:Synthesis,Functionalization And Application In Biomedicine

As cancer is one of the most devastating diseases,chemotherapy is currently the most widely used therapeutic method.However,chemotherapy drugs are not only specifically toxic to tumor cells,but also toxic to all tissues whatever they contact,resulting undesirable side effects and bringing new pain to patients.Therefore,it is urgent to develop much safer treatment paradigms to cure cancer.Nanotechnology can improve the pharmacokinetics and pharmacodynamic properties of drug,and therefore can improve the targeting ability of drugs to tumor.The ultrasmall mesoporous silica nanoparticles?MSNs?hold great potential applications in biomedical fields,such as drug delivery,cell labeling and gene vectors,due to their mesoporous structure,non-toxic,large surface area,versatile surface modification and excretion rapidly via the renal route.Therefore,the ultrasmall MSNs can be used as antitumor drug carrier,which brings hope for the treatment of cancer.Focusing on the application of ultrasmall MSNs in diagnosis and therapy of cancer,this thesis consists of four parts as follows:1)Ultrasmall MSNs were prepared by sol-gel method.Particle size and monodispersity are used as the main evaluation indexes,and the optimal synthesis route was developed:Hexadecyl trimethyl ammonium bromide?CTAB?and ammonium hydroxide were used as template agent and catalyst,respectively;PEG-silane was added as a capping agent.Highly dispersed and stabilized MSNs with uniform particle size?7.29 nm?were prepared.2)Since the original MSNs have limitted application in the biomedical fields,the fluorescent molecules were labeled in the MSNs,which could be used as fluorescence imaging diagnosis.When the molar ratio of dye-silane conjugate?FITC-APTES?to TMOS was 1:40,the obtained PEGylated fluorescent MSNs?FMSNs-PEG?were uniform,with an average size of 8.36 nm.In order to expand the application of FMSNs-PEG,the amino group was funtionalized on their surface.Aminated FMSNs-PEG?FMSNs-PEG-NH₂?show strong positive zeta potential?approximately8.9 mV?in water.3)MSNs are applied as the drug carrier.DOX was loaded on FMSNs and the DOX release profile in vitro was studied.The results showed that the loading capacity of FMSNs,FMSNs-PEG and FMSNs-PEG-NH₂ could reach 550 mg/g,507 mg/g and453 mg/g,respectively.The release profile of DOX was found to be pH sensitive.Furthermore,the cell uptake of FMSNs and FMSNs-PEG were inveatigated by confocal laser scanning microscopy.4)A novel kind of multifunctional nanocarrier,which combined fluorescence imaging and drug delivery,was developed by encapsulating both FMSNs-PEG and DOX within liposome.This nanocarrier combines the merits of both FMSNs-PEG and liposome.FITC was grafted on the surface of MSNs-PEG and can be used as a biocompatible probe for in vivo fluorescent imaging studies.Liposomal membranes could prevent premature drug release.The diameters of blank liposome?FMSNs-PEG@Liposome and FMSNs-PEG@Liposome+DOX were all around 110nm.It demonstrated that encapsulation of FMNPs-PEG and DOX had no effect on the particle size of liposome.The toxicity studies indicated blank liposome and FMSNs-PEG@Liposome had no toxicity within 0.2 mg/mL.Furthermore,we found that the entrapment efficiency of the DOX was increased from 84%to 96%by adding FMSNs-PEG.FMSNs-PEG@Liposome can control drug release.FMSNs-PEG@Liposome can used as a drug delivery system for simultaneous cancer imaging and therapy.