Construction Of Multifunctional Mesoporous Silica Drug Delivery System And Its Application In The Inhibition Of Cancer Cells Viability

Cancer is one of the biggest threats to human health.With the rapid development of nanotechnology,a series of drug controlled release systems based on nanomaterials have been developed to kill cancer.In the dissertation,we designed several novel drug controlled release systems,including a controlled-release system combination of gene interference with chemotherapeutic drugs,a cap-free and rapid biodegraded controlled release system and patch-type controlled release system for lesions.The main points are as follows:1.We introduced miR-31 to bind to 3’ untranslated region of mtEF4,resulting in the downregulation of its messenger RNA and protein to trigger cancer cells apoptosis through mitochondria-related pathway.To achieve better therapeutic effect,a mesoporous silica nanoparticles-based controlled system had been developed.This system was fabricated by conjugation of microRNA-31 onto doxorubicin-loaded mesoporous silica nanoparticles with the surface functionalization and tumor-specific conjugation,and drug release was triggered by acidic environment of tumors.2.We synthesized a drug delivery system with cap-free and pH/redox-responsive properties by coating disulfide-bridged silica shell on CuS nanoparticles.The hydrophobic phenylamine-functionalized nanochannels on silica shell could protect doxorubicin from being wetted by neutral solution in the transport process and release sealed doxorubicin after being protonated in acidic environment of cancer cells.Meanwhile,under the stimulation of plentiful glutathione in A549 cells,the disulfide-bridged structure was biodegradable,which could efficiently increase the intracellular accumulation of doxorubicin and generate high cytotoxicity.3.We developed a smart pH-triggered controlled drug release nanomaterial incorporated into electrospun fibers for the eradication of local cancer recurrence.First,CaCO3-DOX pellets were got by chelate reaction of calcium carbonate with doxorubicin through gas diffusion method,followed by coating with a thin layer of silica to get CaCO3-DOX@SiO2 particles.The CaCO3-DOX@SiO2 particles were then mixed with the PLLA solution to make the electrospinning fibers.This release system was responsive to the weakly acidic condition of the cancer cell because CaCO3 could react with hydrogen ion to release CO2.Under the stimulation of generated CO2,the outer layer of SiO2 and electrospinning fibers would be gradually damaged to release DOX.