Calcium Carbonate Nanoparticles Mediated Specific "Calcicopsotis" Of Tumor Cells And Synergistic Therapeutic Effect

Cancer has always been one of the most difficult diseases for human beings.How to treat cancer is the focus of modern medical research.In biological activities,some ions,such as Na⁺,K⁺,Ca²⁺,play an important role in regulating the physiological state of cells.Recently,the way of which can induce tumor cell death by externally interfere intracellular ion homeostasis has become a new method of cancer treatment.However,single ion or small molecule ionophores have many limitations in actual tumor treatment,such as short circulation time in the body,weak specific recognition ability and limited dose systemic toxicity.In order to solve this problem,research in recent years have shown that completely degradable nano-mineral particles are used in the field of ion interference therapy,due to their combination of biodegradation,ion release function,high biological safety,and inducible multimodal therapy,reflects a huge advantage.At the same time,a single tumor treatment model often has disadvantages such as the treatment effect is not as good as expected,and the tumor is prone to relapse.Therefore,the construction of an anti-tumor nano-platform based on nano-mineral particles for ion interference therapy and other treatment methods has a broad application prospect.In this study,calcium ions,which strictly control the process of cell life,were selected as a means of ion therapy to induce"calcicopsotis"in cells.At the same time,based on the high biocompatibility,high p H response capability,and high calcium ion release capability of nano calcium carbonate particles,Innovatively combine the natural acquisition,rapid preparation,and photothermal advantages of metal polyphenol materials,a kind of"fusiform type"nano calcium carbonate particles coated with TA-Fe（metal polyphenol network,MPN）and“round type”nano calcium carbonate particles coated with EGCG-Fe（MPN）were prepared.In the end,a collaborative anti-tumor nano-platform integrating"calcium death"and photothermal therapy was constructed.The above two nano materials were further studied through the physical properties,biocompatibility,in vitro cytotoxicity and tumor therapy in vivo.Research shows that both types of nanoparticles can significantly increase the Ca²⁺concentration in 4T1 cells,induce Ca²⁺overload in 4T1 cells,and trigger mitochondrial-related apoptosis programs.At the same time,under the influence of synergistic photothermal therapy,the survival rate of 4T1 cells is further reduced.In vivo experiments in mice have shown that,compared with a single photothermal treatment,the"calcicopsotis"effect caused by calcium ion overload and photothermal effect have an excellent synergistic anti-tumor effect.