Synthesis Of Mesoporous Silica Nanorods And The Application In Chemotherapy/Photothermal Therapy/Oxidative Therapy/Starvation Therapy

The morbidity of cancer is on the increase in recent years,cancer becomes one of the major diseases that threaten human health.Traditional therapies still have toxic side effects,so the as-prepared nanosystem selectively toward cancer cells while providing minimal adverse effects and maximal therapeutic efficacy.Constructing targeted drug delivery systems and novel combinational therapy provide efficient methods to solve those problems.Mesoporous silica,is an ideal candidate owing to its excellent biocompatibility,large specific surface area,ordered pore structure,large pore volume,and easy surface chemistry.Mesoporous silica nanorods have attracted remarkable interest because of their higher trans-membrane transport rates.Aspect ratio affects their cellular uptake efficiency and drug loading capability,unfortunately,the formation of precisely controlled aspect ratio is challenging.In addition,starvation therapy has been widely studied in recent years.However,considering it is difficult to completely kill cells by relying solely on starvation therapy because of the catalytic efficiency of glucose oxidase and the metabolism pathways,which hinders the further clinical application.Based on this,the as-prepared mesoporous silica nanorods possess precisely controlled aspect ratio.A systematic comparison was employed to choose the nanocarrier.Afterwards,the cancer cell-targeted nanosystem was established and applied in starvation therapy.Based on the remarkable advantages of mesoporous silica nanorods,in this work,as-prepared the length of mesoporous silica nanorods were approximately 200,300,400,600,800,1000,>1000 nm,respectively,and their width were unchanged?100 nm?is synthesized.In addition,mesoporous silica nanosphere with a diameter of 100 nm.The results showed that the Brunauer-Emmett-Teller surface area of the as-prepared mesoporous silica nanorods with aspect ratio of 6?AR6?was 1021.77 m²/g,the doxorubicin loading capacity was 26.1%.The tests of confocal laser scanning microscopy and flow cytometry analysis indicated that AR6featured a comparatively higher cellular uptake efficiency than the other mesoporous silica nanorods.Based on AR6 possessed the highest cellular uptake efficiency and higher drug loading capacity,AR6-based cancer cell-targeting nanosystems were designed for lysosome dysfunctional synergistic chemotherapy/photothermal therapy/oxidative therapy/starvation therapy.Doxorubicin was encapsulated into the porous channel of AR6.Glucose oxidase was immobilized on the surface of AR6 by electrostatic interaction and then coated with polydopamine.Polyethylene glycol-folic acid was introduced,a lysosome dysfunctional drug?Siramesine?was adsorbed via?-?and electrostatic interaction.At p H 7.4,almost no drug was released.After exposure to the near-infrared irradiation,the percentages of Siramesine and doxorubicin released at p H 5.0 were 95.0%and 90.6%.Confocal laser scanning microscopy,flow cytometry analysis and cytotoxicity tests indicated that under near-infrared irradiation for 600 s,the polydopamine shell triggered photothermal therapy and nanosystem can exceed the critical temperature?43??to elevate the catalytic efficiency of glucose oxidase,which further accelerated intracellular glucose consumption and generated a relatively high level of H₂O₂,which enhanced starvation therapy and oxidative therapies.In addition,Siramesine was employed to inhibit lysosomal metabolism and accompany glucose oxidase to reach a dual-enhanced starvation therapy effect.Under near-infrared irradiation,the developed nanosystem?doxorubicin,2.5?g/m L?showed superior therapeutic efficacy against cancer cells at a relatively low dosage.