Research On The Application Of Nano-materials Inducing Intracellular Ion Interference In Tumor Therapy

To completely cure cancer is still a difficult problem for people.Clinical oncology treatment still requires more effective new protocols for early diagnosis of cancer and new therapies during treatment.At present,as a new and effective anti-tumor technique,ion interference method has received extensive attention.The type and distribution of ions are closely related to the physical and chemical properties and biological effects of cells.Excessive or insufficient ions will seriously affect the normal physiological functions of tumor cells,and even cause tumor death.In this paper,the intracellular ion concentration was interfered by the construction of composite nanoplatforms and the regulation of related protein expression,and the application of these nanoplatforms in tumor treatment was studied.The research results are as follows:Firstly,in order to enhance the interference of Ca²⁺ and related cellular signaling pathways in tumor cells,a nano-platform,which includes UCNPs-Ce6@Ru R@m Si O₂@PL-HA NPs（UCRSPH）and SA-Ca O₂ nanoparticles,was prepared for improving the tumor micro-environment（TME）,alleviating tumor hypoxia,disturbing Ca²⁺ signal as well as enhancing photodynamic tumor therapy（PDT）.UCRSPH combined with SA-Ca O₂ can alter TME and relieve hypoxia of the tumor to realize self-reinforcing PDT under near-IR irradiation（980 nm）.The ruthenium red（Ru R）in the UCRSPH NPs can be released to the cytoplasm after endocytosis of the nanoparticles,target Ca²⁺ channel proteins on the endoplasmic reticulum and mitochondria,sarcoplasmic reticulum Ca²⁺-ATPase（SERCA）,and mitochondrial calcium uniporter（MCU）.The combined participation of nanoparticles and Ru R promote Ca²⁺ imbalance and cytoplasmic calcium overload with the assistance of Ca O₂,and provide tumor cells higher sensitivity to PDT.In addition,the nanoplatform has fluorescence imaging and calcification computed tomography（CT）imaging capabilities,which have important guiding significance for in vivo therapy.In conclusion,by improving TME selfreinforcing PDT and Ca²⁺ signaling interference,this image-guided nanoplatform show the potential for a highly specific and efficient combination therapy for tumor cells while exhibiting minimal side effects on normal cellsSecondly,in order to enhance the interference of Cl^-and related cell signaling pathways in tumor cells, Cl O₂-loaded nanoparticles（Metformin（Me）& Fluvastatin sodium（Flu）& Bupivacaine（Bup）&Cl O₂@Ca Si O3@Mn O₂-arginine-glycine-aspatic acid（RGD）,MFBC@CMR NPs）were prepared.After outer layer Mn O₂ was degraded in the high glutathione（GSH）TME,MFBC@CMR NPs released metformin（Me）to target the mitochondria,thus interfering with the tricarboxylic acid（TCA）cycle and promoting the production of lactate.In addition,released fluvastatin sodium（Flu）by the NPs acted on monocarboxylic acid transporter 4（MCT4）in the cell membrane to inhibit lactate leakage and induce a decrease of intracellular p H,further prompting the NPs to release chlorine dioxide（Cl O₂）,which then oxidized methionine,inhibited tumor growth.More importantly,nano-platforms produce large amounts of chloride ions Cl^-in the cytoplasm.Cl^-couldenter mitochondria through the voltage-dependent anion channel（VDAC）channel,which was opened by bupivacaine（Bup）.The disruption of Cl^-homeostasis promotes mitochondrial damage and membrane potential decline,leading to the release of cytochrome C（Cyt-C）and apoptosis inducing factor（AIF）and further inducing cell apoptosis.To sum up,the p Hregulating and Cl O₂-loaded MFBC@CMR nano-platform can achieve cascade chlorine treatment and methionine-depletion starvation therapy toward tumor cells,which is of great significance for improving the clinical tumor treatment effect.To sum up,this study constructed the two independent nano materials,respectively the interference of Ca²⁺ and Cl^-related cell signaling pathways,and through the nano materials on the improvement of the TME and tumor in situ imaging technology,effectively improve the effect of tumor therapy,the construction of a new method for tumor treatment and clinical treatment of the development of new strategies has important theory meaning.