Magnetic Nanoplatform For Tumor Imaging And Specific Chemodynamic Therapy

Currently,cancer is one of the most serious diseases that threaten human life.Chemodynamic therapy(CDT)based on reactive oxygen species(ROS)is rapidly emerging as a novel and effective strategy for cancer therapy.However,the efficacy of CDT is greatly limited by the lack of acidity in tumor and the“off-target”toxicity of nanomedicines.To solve these problems,we developed a novel tumor microenvironment-responsive magnetic nanoplatform that can“turn on”the catalytic activity of FePt@FeOx in cancer cells and increase the acidity of cancer.Therefore,the magnetic nanoplatform overcomes the problem of insufficient tumor acidity and poor specificity caused by“off-target”toxicity,which achieves excellent effect for CDT and provides a new strategy for highly effective and specific cancer therapy.The main research contents of this paper as following:(1)Develop high-effective and acidity-activated magnetic nanoplatform for CDT.We developed a highly efficient catalyst FePt@FeOx with core-shell structure to improve the catalytic activity of Fenton reaction.Based on the acidity-activated characteristics of the chemotherapeutic drug tamoxife n(TAM),FePt@FeOx nanoparticles were self-assembled with TAM to construct an acidity-activated magnetic nanoplatform(FePt@FeOx@TAM-PEG).The chemotherapeutic drug TAM improves the ability of magnetic nanoplatforms to respond to dissociation under acidic conditions.FePt@FeOx converts hydrogen peroxide(H₂O₂)into highly toxic hydroxyl radical(·OH)under acidic conditions,which improves the efficiency of Fenton reaction.In this chapter,the physicochemical properties of magnetic nanoplatforms provides important support for subsequent biological research.(2)Regulate tumor acidity and enhance CDT through cyclic catalytic strategy.The acidity-response characteristics of TAM enable to"turn on"the catalytic activity of FePt@FeOx@TAM-PEG magnetic nanoplatform in acidic tumor microenvironment,while the catalytic activity remains silent in neutral conditions.Importantly,the release of TAM within tumor cells inhibits mitochondrial complex I,leading to an upregulation of lactate content,thereby increasing the acidity of tumor and overcoming the limitation of insufficient acidity in tumor of CDT.The increased acidity of tumor further promotes the decomposition of FePt@FeOx@TAM-PEG.Through the positive feedback loop,the magnetic nanoplatform releases a la rge number of FePt@FeOx nanocatalysts,which can efficiently catalyze H₂O₂ under more acidic conditions,thus significantly improving the efficiency of Fenton reaction and enabling the boost generation of ROS in tumor for achieving highly effective tumor t herapy.In this paper,through developing the acidity-activated cyclic catalytic magnetic nanoplatform,the highly efficient and specific chemodynamic therapy has been realized,which provides a new approach for enhancing tumor catalytic therapy and reducing“off-target”toxicity to normal tissues.