Application And Research Of Mesoporous Silica And PAAs@Inorganic Nanoparticles In The Drug Delivery Systems

In this thesis,several drug delivery systems combining chemotherapy,targeting and MRI imaging were researched,which were based on the mesoporous silica nanoparticles(MSNs)and polyacrylic acid sodium-inorganic nanoparticle assembly(PAAs@Inorganic nanoparticles,PAAs@INPs).The release mechanisms could be triggered by pH,redox and glucose in tumor microenvironment.The thesis was divided into three chapters:In chapter 1,the preparation and application in nano-biomedicine of MSNs and PAAs@INPs as drug carriers were introduced in detail.Also,the research purpose and content of this dissertation were described in brief.In chapter 2,two kinds of drug delivery systems based on the MSNs were established.(1)By self-assembly,amidation and modification of L-selenocystine(DSeCys)and ZnO-NH2 nanoparticles on the surface of MSNs,drug delivery system of MSN-DSeCys-ZnO was synthesised.Data in vitro release experiments demonstrated that this drug delivery system could be released by H2O2,DTT and pH triple stimulus response.The result from MTT assay showed that the HeLa cell inhibition rate reached 86.29%,indicating that this drug delivery system could effectively inhibit the growth of tumor cells and achieve synergistic therapeutic effects in response to these triple stimuli.(2)The drug delivery system based on MSN-CBA-PVA nanocomposites was obtained by modification of CBA molecule on MSNs,followed combining PVA molecule through borate ester bond.The leakage was only 12.74%in buffer solution(pH=7.4)after 48h,indicating the MSNs could be well sealed by the PVA molecule.The release of DOX was found to 83.65%under triple stimulation including pH,glucose and H2O2.Data from MTT experiments showed that the cell inhibition rate was as high as 84.74%in the presence of MSN-CBA-DOX-PVA nanocomposites.In chaper 3,the PAAs spheres were used as template to synthesis PAAs@inorganic nanoparticles by electrostatic adsorption of metal ions and precipitation process.(1)PAAs@MnO(OH)-RGD drug delivery system was established and the nanocomposites had very high drug loading rate(91.1%).In the presence of reducing agents or in the acidic condition,the above nanocomposites was dissociated and released out of Mn2+ and drug.Therefore,a multifunctional theranostic system combining MRI imaging,drug delivery and targeted treatment could be achieved based on the PAAs@MnO(OH)-DOX-RGD nanoparticles.The drug release was reached to 88.79%in the addition of 2mM DTT and in pH=5.0 buffer.After internalization into HeLa cells,the inhibition reached to 76.58%with only 5.5μg/ml of PAAs@MnO(OH)-DOX-RGD nanoparticles.The results from the in vitro magnetic resonance imaging showed that r1 value of the composites could reach to 10.62 mM-1·S-1 in buffer solution of pH = 5.0+5mM DTT;(2)A pH responsed drug delivery system based on PAAs@CaP nanocomposites was studied.Premature release at pH=7.4 was only 9.47%,however,the release at pH=5.0 was found to be 80.6%,demonstrating that the obtained PAAs@CaP nanocomposites were easy dissolved in the acidic condition.MTT results exhibited that the cell inhibition was 89.79%with 5.72μg/ml of PAAs@CaP-DOX-RGD nanocomposites.