Functionalized G-C₃N₄ Nanosheets With Piezo-fenton Catalytic Properties And Their Chemodynamic Therapy For Tumors

Cancer,a serious health problem,has attracted the attention of doctors and researchers around the world.There are various treatments available to treat cancer,such as surgical resection,chemotherapy and radiotherapy,as well as the emerging photodynamic therapy（PDT）,photothermal therapy（PTT）and sonodynamic therapy（SDT）,but these treatments still have some drawbacks.The biggest disadvantage of traditional cancer treatment is the serious side effects,while the emerging therapies PDT and PTT face the problem of poor tissue penetration of light and SDT has the disadvantage of low ROS production.The weakly acidic and H₂O₂ overexpressing in tumor microenvironment provides the ground for the development of another emerging therapy—chemodynamic therapy（CDT）,which is based on the Fenton reaction to produce·OH to kill tumor cells,which only involves the conversion of chemical energy.This not only helps to reduce the side effects of the treatment process,but also avoids the limitations of the equipment and the lack of light penetration ability,and also has a relatively high efficiency of Reactive Oxygen Species（ROS）generation.In order to further enhance CDT,nanomaterials are currently being designed to achieve this in terms of H₂O₂ supply,catalytic performance,p H reduction and the introduction of external energy fields.g-C₃N₄ is a two-dimensional semiconductor material with a medium band gap containing only carbon and nitrogen atoms,which has been extensively investigated for biological applications due to its biocompatibility and low toxicity.Because of the ordered arrangement of triangular holes in the structure,the thin layer of g-C₃N₄ nanosheets can therefore be piezoelectrically catalyzed by coupled piezoelectric effects,which allow electron-hole separation to occur under ultrasound（US）and thus catalyze the oxidation of H₂O and O₂ to highly reactive H₂O₂.Based on this,we have designed a nanoplatform with in situ H₂O₂supply,Fe³⁺/Fe²⁺cycling and external energy input to enhance the Fenton reaction,which can then be used to for tumour CDT.The research in this paper is as follows.1:Modification of g-C₃N₄ nanosheets and their piezoelectric-Fenton catalytic properties under USIn Chapter 2,Fe-g-C₃N₄nanosheets and Au-Fe-g-C₃N₄ nanosheets were obtained by modifying g-C₃N₄ nanosheets,and it was found that the ROS generation ability of Au-Fe-g-C₃N₄ nanosheets was superior to Fe-g-C₃N₄ nanosheets and g-C₃N₄ nanosheets.Au-Fe-g-C₃N4 nanosheets had the ability to produce H₂O₂ under US and can consume H₂O₂ by in situ Fenton reaction.The excellent ROS generation ability of Au-Fe-g-C₃N₄ nanosheets is associated with narrower band gap,lower valence band,reduced electron-hole complexation ability,lower electrochemical impedance and more ultrasonically excited electrons.Finally,based on these experimental results,the enhancement mechanism of ROS production of Au-Fe-g-C₃N₄ nanosheets under US is proposed.2:Peptide-modified Au-Fe-g-C₃N₄ nanosheets materials for tumor CDT therapyIn Chapter 3,P-Au-Fe-g-C3N4 nanosheets were obtained by modifying the biocompatible PEG₂₀₀₀ and the targeting peptide CYEVHTYYLD on Au-Fe-g-C₃N₄nanosheets.Lysosomal co-localization assay showed that human colon cancer cells HCT-116 uptake P-Au-Fe-g-C₃N₄ nanosheets by endocytosis.Cytotoxicity assay,cell live-dead staining assay and apoptosis showed that P-Au-Fe-g-C₃N₄ nanosheets exhibited efficient killing ability against HCT-116 cells under US with an IC₅₀ of 92.22μg/m L,which was related to its ability to produce a large amount of ROS at the cellular level,and finally the experiments demonstrated that P-Au-Fe-g-C₃N₄ nanosheets have good biosafety.In conclusion,P-Au-Fe-g-C₃N₄ nanosheets obtained based on g-C₃N₄ nanosheets modification and peptide modification exhibited excellent H₂O₂ and ROS production under US,and they showed efficient killing of HCT-116 cells under sonication with an IC₅₀ of92.22μg/m L,while the material exhibited good biosafety.Finally,this work provides a new idea for the design of nanoplatforms based on the Fenton catalytic properties of g-C₃N₄nanosheets under US,and develops a new strategy to improve the efficacy of CDT.