Yang Li, Jinyan Lin, Yueyang He, Kaiyuan Wang, Cailin Huang, Ruifeng Zhang, Xiaolong Liu
{"title":"Tumour-microenvironment-responsive Na2S2O8 nanocrystals encapsulated in hollow organosilica–metal–phenolic networks for cycling persistent tumour-dynamic therapy","authors":"Yang Li, Jinyan Lin, Yueyang He, Kaiyuan Wang, Cailin Huang, Ruifeng Zhang, Xiaolong Liu","doi":"10.1002/EXP.20230054","DOIUrl":null,"url":null,"abstract":"<p>Traditional tumour-dynamic therapy still inevitably faces the critical challenge of limited reactive oxygen species (ROS)-generating efficiency due to tumour hypoxia, extreme pH condition for Fenton reaction, and unsustainable mono-catalytic reaction. To fight against these issues, we skilfully develop a tumour-microenvironment-driven yolk-shell nanoreactor to realize the high-efficiency persistent dynamic therapy via cascade-responsive dual cycling amplification of •SO<sub>4</sub><sup>−</sup>/•OH radicals. The nanoreactor with an ultrahigh payload of free radical initiator is designed by encapsulating the Na<sub>2</sub>S<sub>2</sub>O<sub>8</sub> nanocrystals into hollow tetra-sulphide-introduced mesoporous silica (HTSMS) and afterward enclosed by epigallocatechin gallate (EG)-Fe(II) cross-linking. Within the tumour microenvironment, the intracellular glutathione (GSH) can trigger the tetra-sulphide cleavage of nanoreactors to explosively release Na<sup>+</sup>/S<sub>2</sub>O<sub>8</sub><sup>2</sup><b><sup>−</sup></b>/Fe<sup>2+</sup> and EG. Then a sequence of cascade reactions will be activated to efficiently generate •SO<sub>4</sub><sup>−</sup> (Fe<sup>2+</sup>-catalyzed S<sub>2</sub>O<sub>8</sub><sup>2</sup><b><sup>−</sup></b> oxidation), proton (•SO<sub>4</sub><sup>−</sup>-catalyzed H<sub>2</sub>O decomposition), and •OH (proton-intensified Fenton oxidation). Synchronously, the oxidation-generated Fe<sup>3+</sup> will be in turn recovered into Fe<sup>2+</sup> by excessive EG to circularly amplify •SO<sub>4</sub><sup>−</sup>/•OH radicals. The nanoreactors can also disrupt the intracellular osmolarity homeostasis by Na<sup>+</sup> overload and weaken the ROS-scavenging systems by GSH exhaustion to further amplify oxidative stress. Our yolk–shell nanoreactors can efficiently eradicate tumours via multiple oxidative stress amplification, which will provide a perspective to explore dynamic therapy.</p>","PeriodicalId":72997,"journal":{"name":"Exploration (Beijing, China)","volume":"4 2","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2023-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/EXP.20230054","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Exploration (Beijing, China)","FirstCategoryId":"1085","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/EXP.20230054","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
Abstract
Traditional tumour-dynamic therapy still inevitably faces the critical challenge of limited reactive oxygen species (ROS)-generating efficiency due to tumour hypoxia, extreme pH condition for Fenton reaction, and unsustainable mono-catalytic reaction. To fight against these issues, we skilfully develop a tumour-microenvironment-driven yolk-shell nanoreactor to realize the high-efficiency persistent dynamic therapy via cascade-responsive dual cycling amplification of •SO4−/•OH radicals. The nanoreactor with an ultrahigh payload of free radical initiator is designed by encapsulating the Na2S2O8 nanocrystals into hollow tetra-sulphide-introduced mesoporous silica (HTSMS) and afterward enclosed by epigallocatechin gallate (EG)-Fe(II) cross-linking. Within the tumour microenvironment, the intracellular glutathione (GSH) can trigger the tetra-sulphide cleavage of nanoreactors to explosively release Na+/S2O82−/Fe2+ and EG. Then a sequence of cascade reactions will be activated to efficiently generate •SO4− (Fe2+-catalyzed S2O82− oxidation), proton (•SO4−-catalyzed H2O decomposition), and •OH (proton-intensified Fenton oxidation). Synchronously, the oxidation-generated Fe3+ will be in turn recovered into Fe2+ by excessive EG to circularly amplify •SO4−/•OH radicals. The nanoreactors can also disrupt the intracellular osmolarity homeostasis by Na+ overload and weaken the ROS-scavenging systems by GSH exhaustion to further amplify oxidative stress. Our yolk–shell nanoreactors can efficiently eradicate tumours via multiple oxidative stress amplification, which will provide a perspective to explore dynamic therapy.