Mesoporous Silica-based Multifunctional Response Drug Carrier And Its Targeted Controlled Release Properties

Chemotherapy is the most common treatment for cancer.At present,there are more than 50 different types of chemotherapy drugs,which can be used for routine tumor treatment.However,due to their low bioavailability and severe side effects of the drug,the therapeutic effect is not satisfactory.Therefore,the study of drug delivery function vectors and new methods of tumor therapy,improving drug utilization,reducing toxic and side effects and improving curative effect is of great significance for the treatment of tumors.In this paper,the multifunction electric field response drug transport system was prepared and the drug controlled release and tumor treatment performance were characterized.We used mesoporous silica nanoparticles as the drug nanocontainer,and designed a dual responsive targeted drug delivery system based on smart polymer coated mesoporous silica for cancer therapy.The system uses the target molecules to target the pathological parts actively,and then uses the functional response molecules to control the drug release,and thus realize the fixed-point,timed and quantitative release of drugs.It can reduce the toxic and side effects of drugs on normal cells,and improve the therapeutic effect.The main results obtained were summarized as follows:(1)Mesoporous silica nanoparticles(MSNs)were chosen as carriers,the silane coupling agent 3-(isobutene oxygen)propyl silane(MPS)was introduced into the MSNs surface by condensation reaction.The electric field responsive units were coalesced in poly(nitrophenylmethacrylate-co-methacrylicacid-co-methacryloxy propyltrimethoxysilane)(NPMA),which is coated the surface of mesoporous silica nanospheres to form a dual responsive drug delivery system.Finally,folic acid(FA)molecules were further attached to the nanocarrier for active targeting specific 4T1 cells with folate-receptors.Using anticancer drug doxorubicin(DOX)as template drug molecule,the release behavior of drugs under different low frequency pulsed electric fields conditions was studied.Subsequently,the drug release kinetics of the system under different conditions was studied,and the release mechanism of the sample was analyzed.Finally,the biocompatibility and active targeting function of the samples were studied by using 4T1 breast cancer cells.It is found that the drug carrier not only has good biocompatibility but also can target tumor cells accurately.The killing force of the carrier of the drug on the cancer cell 4T1 cells under different low frequency pulsed electric fields was also studied.It was found that the cell survival rate of the drug carrier with low frequency pulsed electric field was 31.1%,which showed strong cytotoxicity.Finally,the biocompatibility and tumor suppressor effect of the body were evaluated by animal experiments.It was found that the drug carrier has good biocompatibility in the body,and the tumor suppressor rate in the body can reach 73%.(2)Mesoporous silica nanoparticles(MSNs)were chosen as carriers,the silane coupling agent 3-(isobutene oxygen)propyl silane(MPS)was introduced into the MSNs surface by condensation reaction.The electric field and temperature responsive units were coalesced in methacrylic acid ester of p-nitrophenol(NPMA)and Nisopropyl methyl acrylamide(NIPAM),which is coated the surface of mesoporous silica nanospheres(MSNs)to form a dual responsive drug delivery system(DFMS).Using anticancer drug doxorubicin(DOX)as template drug molecule,the release behavior of the drug under different low frequency pulsed electric field and temperature was studied.Subsequently,the drug release kinetics of the system under different conditions was studied,and the release mechanism of the sample was analyzed.Finally,the biocompatibility of MCF-7 cell and the response to electric field were studied.