Single-atom nanozymes(SANzymes)with multi-mimetic activities capable of altering the cellular redox balance demonstrate significant potential in tumor therapy.However,the catalytic treatment provided by SANzymes alone...Single-atom nanozymes(SANzymes)with multi-mimetic activities capable of altering the cellular redox balance demonstrate significant potential in tumor therapy.However,the catalytic treatment provided by SANzymes alone is insufficient to achieve optimal outcomes.Therefore,the combination of nanozyme catalysis with drug therapy is considered a promising alternative.Nonetheless,the leakage of drug molecules is a primary cause of chemotherapy resistance in cancer treatment.Consequently,developing novel drug immobilization methods to attach them to SANzymes is expected to enable multimodal synergistic therapy.Herein,a multifunctional nanoplatform is designed by modifying bioinspired PDA on iron-based SANzyme(Fe SANzyme)and immobilizing doxorubicin(DOX)through Michael addition/Schiff base reaction,which greatly promotes the drug loading efficiency.The Fe SAN-PDA@DOX@HA displays controllable drugs release behavior in the tumor microenvironment(TME),where the Fe SAN-PDA nanozyme can catalyze high level of H_(2)O_(2)to produce oxygen to alleviate hypoxia,convert H_(2)O_(2)to the toxic reactive oxygen species(ROS),and deplete intracellular glutathione via the catalase(CAT),peroxidase(POD),and glutathione oxidase(GSHOx)-like activities,respectively.The high drug loading,exceptional nanozyme catalysis,combined with the good photothermal performance of Fe SAN-PDA,resulted in sustained chemodynamic/photothermal/chemotherapy in a mouse mammary carcinoma model.The results reveal the synergistic antitumor potential of the novel conjugation of DOX on Fe SANzyme via PDA,offering a strategy for drug immobilization,TME remodeling and synergistic multimodal therapy.展开更多
基金supported by the National Natural Science Foundation of China(22274047,21974042,22274048)the Scientific Research Fund of Hunan Provincial Education Department(18A010)+2 种基金the Science and Technology Department of Hunan Province(2021JJ30012)the Hubei Science and Technology Program(2022CFB781)the Innovation Team of Hubei University of Science and Technology(2023T13)。
文摘Single-atom nanozymes(SANzymes)with multi-mimetic activities capable of altering the cellular redox balance demonstrate significant potential in tumor therapy.However,the catalytic treatment provided by SANzymes alone is insufficient to achieve optimal outcomes.Therefore,the combination of nanozyme catalysis with drug therapy is considered a promising alternative.Nonetheless,the leakage of drug molecules is a primary cause of chemotherapy resistance in cancer treatment.Consequently,developing novel drug immobilization methods to attach them to SANzymes is expected to enable multimodal synergistic therapy.Herein,a multifunctional nanoplatform is designed by modifying bioinspired PDA on iron-based SANzyme(Fe SANzyme)and immobilizing doxorubicin(DOX)through Michael addition/Schiff base reaction,which greatly promotes the drug loading efficiency.The Fe SAN-PDA@DOX@HA displays controllable drugs release behavior in the tumor microenvironment(TME),where the Fe SAN-PDA nanozyme can catalyze high level of H_(2)O_(2)to produce oxygen to alleviate hypoxia,convert H_(2)O_(2)to the toxic reactive oxygen species(ROS),and deplete intracellular glutathione via the catalase(CAT),peroxidase(POD),and glutathione oxidase(GSHOx)-like activities,respectively.The high drug loading,exceptional nanozyme catalysis,combined with the good photothermal performance of Fe SAN-PDA,resulted in sustained chemodynamic/photothermal/chemotherapy in a mouse mammary carcinoma model.The results reveal the synergistic antitumor potential of the novel conjugation of DOX on Fe SANzyme via PDA,offering a strategy for drug immobilization,TME remodeling and synergistic multimodal therapy.
