Construction And Anti-tumor Effect Of Nano Drug Delivery Systems Based On Mesoporous Silica Nanoparticles

Mesoporous silica nanoparticles(MSN)are widely used in the construction of nano drug delivery systems(NDDS)due to their controllable internal pore size,high drug loading capacity,and excellent biocompatibility.These NDDS show great prospects in the diagnosis and clinical trial of diseases.In this thesis,we designed and fabricated two types of MSN-based NDDS,which possessed rational designed multi-responsive characteristics,to improve the therapeutic selectivity and efficacy of cancer by combining the unique tumor microenvironment(TME)and external stimulus.The thesis mainly includes the following two aspects:In the first section,we constructed a dual-responsive MSN-based nanocarrier and studied their antitumor activity.Primarily,MSN with a particle size of about 60 nm was prepared and decorated with β-cyclodextrin(β-CD)through disulfide bond.Then,methyl polyethylene glycol(mPEG)was introduced onto the surface of MSN via hostguest interactions between β-CD and azobenzene to obtain UV/redox dual-responsive MSN-ss-CD/mPEG.The morphological results showed that the particles were uniform and well-dispersed.The average size increased to about 227 nm.The nanocarrier loaded with the model anticancer drug doxorubicin(DOX)exhibited a response to UV irradiation and redox stimulus,showing a controllable drug release behavior.In the presence of both UV and redox stimuli,the cumulative DOX release amount of the carrier at 48 h reached 53.8%,which was 4 times higher than that of the non-stimulation group.The findings in the investigation of cellular endocytosis and in vitro anti-tumor efficacy showed that the DOX@MSN-ss-CD/mPEG exhibited good selectivity and increased the inhibition of cancer cells.In the second section,we fabricated a dual-responsive MSN with not only UV/redox dual responsibility but also hepatocarcinoma targeting capability,based on the previous work.By using the MSN decorated with β-CD as the host and a polymerized galactose/azobenzene-grafted polymer(GAP)as the guest,a galactose coated MSN-ssCD/GAP was achieved.The morphological test showed that the particles were uniform and well-dispersed with a diameter at about 124 nm.The drug release research demonstrated that the nanocarrier could release the drug rapidly under UV and redox dual-stimuli.The cumulative release rate within 48 h reached 51.24%,which is 24.63%,8.19%,and 37.36% higher than that of UV,redox,and non-stimulation group,respectively.The surface glycosylated nanocarrier could efficiently deliver DOX into HepG2 cells and exhibited enhanced cytotoxicity in response to the designed stimuli.The half maximal inhibitory concentration(IC50)values of the DOX-loaded nanocarrier against HepG2,HeLa,and COS7 cells were 2.05,3.75,and 6.60 mg/L,respectively,under the combination of UV irradiation and high glutathione concentration,showing good selectivity and biocompatibility.The constructed MSNss-CD/GAP was promising for targeted hepatocarcinoma chemotherapy.