Construction Of Highly Migrating Mesoporous Nanomotors And Application In Photodynamic And Gas Synergistic Therapy For Breast Cancer

The presence of dense extracellular matrix and high tissue hydrostatic pressure in tumor tissues limit the transport of nanoparticles in tumor,resulting in the accumulation of therapeutic drugs mainly in the peripheral regions of solid tumors,making delivery to deeper tumor tissues difficult,which greatly limits the efficacy of tumor therapy.As drug carriers,micro/nanomotors that can actively migrate,easily functionalized and biocompatible are expected to cross the biological tissue barrier,improve the tissue permeability of drugs,and efficiently deliver drugs to tumor sites and even deeper tissues to enhance antitumor efficacy.Accordingly,a novel mesoporous motor was constructed to achieve efficient drug loading and enhance cell uptake,thereby enhancing the efficacy of photodynamic therapy and gas therapy for breast cancer.The main research contents include:1.mesoporous motors for enhanced photosensitizer tumor distribution and its photodynamic therapy efficacyThe traditional nanoplatform haven’t the characteristics of autonomous migration,which makes the permeability of drugs poor during transportation,resulting in insufficient drug accumulation in the deep part of the tumor,which in turn limits the therapeutic efficacy of tumors.In this section,we prepared a Janus structure mesoporous nanomotor by growing mesoporous organic silica on one side of mesoporous platinum nanoparticles.Then,the photosensitizer zinc phthalocyanine was loaded to successfully construct the tumor photodynamic therapy platform（JMP-Gd-ZnPc）.Mesoporous nanomotors could loaded up to 157μg/mg of zinc phthalocyanine（ZnPc）.In vitro hemolysis and cell experiments showed that JMP-Gd-ZnPc had lower hemolysis rate and good biocompatibility.The results of confocal images and multicellular spheroids showed that JMP-Gd-ZnPc enhanced the efficiency of cell uptake and enhanced the depth of tumor tissue penetration.In vivo anti-tumor experiments showed that JMP-Gd-ZnPc could significantly inhibited tumor growth and had excellent PDT effects.2.Construction of cascade amplification gas motor and its antitumor studyGas therapy has been widely used in tumor treatment research.However,the production,concentration and controllable release of therapeutic gases seriously restrict the therapeutic efficacy of tumors.In this part of the work,we use macroporous organic silica nanoparticles to loaded L-arginine,ammoniaborane,and modified copper peroxide nanodots to constructed a cascade amplified gas-producing nanoplatform（LMONs@AB@L-Ag-CuO₂）for the synergistic treatment of H₂ and NO for breast cancer.The nanoplatform has a size of approximately 275 nm,good dispersion and biocompatibility.The hemolysis rate of LMONs@AB@L-Ag-CuO₂ at a concentration of 400μg/m L was only 0.55%,indicating good biological safety.The results of in vitro anti-tumor experiments and ROS and hypoxia-inducible factor HIF-1αshowed that LMONs@AB@L-Ag-CuO₂ could effectively inhibit breast cancer cell growth.