Construction Of Tumor Microenvironment Responsive Iron-manganese Silicate Nanoparticles And Its Application In Tumor Diagnosis And Treatment

Cancer is seriously threatening human health,and the morbidity and mortality are also increasing year by year.Since traditional antitumor treatments fail to significantly improve the efficacy,there is an urgent need to find new treatment modalities.In recent years,the tumor microenvironment has become one of the research hotspots.Here,we designed and synthesized a tumor-microenvironment-responsive composite iron-manganese silicate nanoparticle that can kill tumor cells by regulating the tumor microenvironment and inducing ferroptosis.The nanoparticles compose of PEGylation iron-manganese silicate nanoparticles as the carrier,wherein growth-transforming factor receptor I inhibitor(TGF-β inhibitor)can be loaded inside the pores.After intravenous injection,the nanoparticles reach the tumor site through the EPR effect.In acidic tumor microenvironment,TGF-β inhibitors are rapidly released.The inhibitors can induce M2 macrophages that promote tumor growth and invade to proinflammatory M1 macrophages,thereby increasing concentration of H2O2 at the tumor area.The iron ions released under acidic conditions can react with H2O2 through Fenton reaction,and resulting in accumulation of hydroxyl radicals(·OH)which cause ferroptosis to kill tumor cells.At the same time,the manganese ions released by the nanoparticles can react with H2O2 to generate oxygen,thereby improving the hypoxic state of the tumor area.In addition,the released manganese and iron ions can be used in synergistic T1-T2 dual-modal magnetic resonance imaging to enhance contrast and achieve accurate monitoring of tumor tissue.Therefore,iron manganese silicate nanoparticles can be used as a highly efficient and multifunctional cancer diagnosis and treatment platform,and ferroptosis treatment based on remodeling tumor microenvironment is expected to become a new strategy for tumor treatment.