Periodic Mesoporous Organosilica Mediated Theranostics For Triple Negative Breast Cancer

Triple-negative breast cancer(TNBC)is a subtype of breast cancer that lacks any of three types of receptor proteins(ER/PR/HER-2)and is the most aggressive subtype of breast cancer with a high metastatic rate and poor prognosis.Complete eradication of highly aggressive triple negative breast cancer(TNBC)remains a notable challenge today.In recent years,phototherapy based on nanomaterials is a new method of cancer treatment,with a wide range of clinical applications.In this dissertation,two novel nanocomposites based periodic mesoporous organosilica have been used to study the enhanced photodynamic therapy(PDT)and imaging-guided photothermal-chemotherapy for triple negative breast cancer treatment.1)We have firstly constructed a multi-functional nano-platform of yolk-shell structure of periodic mesoporous organosilica coupled Chlorin e6(Ce6)and catalase(Catalase)for enhanced photodynamic therapy of triple negative breast cancer treatment.The multi-functional nano-platform based yolk-shell structure of periodic mesoporous organosilica coupled with Chlorin e6 and catalase(Yolk-Shell PMO-Ce6@Catalase)has an organic-inorganic hybrid skeleton structure,Uniform size,good stability and biocompatibility.In vitro experiments,the results show that the nanoplatform has good singlet oxygen generation ability.Catalase can convert H2O2 into O2,increasing the concentration of oxygen around the cells,and solve the problem of hypoxia in the tumor,beneficial to enhancing the photodynamic therapy effect.Compared with free Ce6 and Yolk-Shell PMO-Ce6 photodynamic therapy,the results of in vivo experiments show that the photodynamic therapy of Yolk-Shell PMO-Ce6@Catalase nano-platform can significantly inhibit tumor growth.Histopathological results also reveal that the enhanced PDT can form the most extensive apoptotic and necrotic cells in the tumor area.Meanwhile,the histopathological results reveal that the photodynamic therapy doesn't produce significant side effects on the main organs.Therefore,we believe that Yolk-Shell PMO-Ce6@Catalase nano-platform in the photodynamic therapy for triple negative breast cancer has great clinical potential.2)An imaging-guided photothermal-chemotherapy strategy for TNBC is developed for the first time based on a periodic mesoporous organosilica(PMO)coated Prussian blue(PB@PMO)nanoplatform.The PB@PMOs have organic-inorganic hybrid frameworks,uniform diameter(125 nm),high surface area(866 m2 g-1),large pore size(3.2 nm),excellent photothermal conversion capability,high drug loading capacity(260 ?g mg-1),and magnetic resonance(MR)and photoacoustic(PA)imaging abilities.The MR and PA properties of the PB@PMO are helpful for imaging the tumor and showing the accumulation of the nanoplatform in the tumor region.The bioluminescence intensity and tumor volume of the MDA-MB-231-Luc tumor-bearing mouse model demonstrate that TNBC can be effectively inhibited by the combined photothermal-chemotherapy,compared to monotherapy strategy.Histopathological analysis further reveals that the combination therapy results in most extensive apoptotic and necrotic cells in the tumor without inducing obvious side effect to major organs.Therefore,the PB@PMO nano-platform with dual-modal PA/MR imaging capability and photothermal-chemotherapeutic property has great clinical application in the treatment of triple negative breast cancer.