Lei Shi, Yao‐Jia Ma, Xing‐Hui Ren, Zheng‐Chen Su, Xi‐Wen He, Wen‐You Li, Yu‐Kui Zhang
{"title":"H2O2 Self‐Supplied Chemodynamic Nanosystem Enhanced by Ca2+ Interference and Starvation Strategy for Targeted Cancer Therapy","authors":"Lei Shi, Yao‐Jia Ma, Xing‐Hui Ren, Zheng‐Chen Su, Xi‐Wen He, Wen‐You Li, Yu‐Kui Zhang","doi":"10.1002/ppsc.202400068","DOIUrl":null,"url":null,"abstract":"Chemodynamic therapy (CDT) has received increasing attention in recent years due to its effectiveness and specificity. However, the limited endogenous hydrogen peroxide (H<jats:sub>2</jats:sub>O<jats:sub>2</jats:sub>) concentration and resistance to reactive oxygen species in cancer cells hinder the further application of CDT. Here, an H<jats:sub>2</jats:sub>O<jats:sub>2</jats:sub> self‐supplied nanosystem FCaO<jats:sub>2</jats:sub>@ZIF‐67‐2‐DG‐FA (FZDF) is synthesized to achieve efficient CDT improvement by Ca<jats:sup>2+</jats:sup> overload and starvation therapy. Under folic acid‐mediated tumor targeting and endocytosis, the ZIF‐67 layer of FZDF is cleaved in the mildly acidic environment, releasing Co<jats:sup>2+</jats:sup> and 2‐deoxy‐D‐glucose (2‐DG). The decomposition of exposed FCaO<jats:sub>2</jats:sub> generates sufficient H<jats:sub>2</jats:sub>O<jats:sub>2</jats:sub>, which further produces abundant <jats:sup>•</jats:sup>OH via the Fenton‐like reaction of Co<jats:sup>2+</jats:sup>. Simultaneously, Ca<jats:sup>2+</jats:sup> overload‐triggered mitochondrial dysfunction couples with glycolysis inhibition via 2‐DG‐induced starvation, which disrupts intracellular adenosine triphosphate (ATP) synthesis and amplifies the efficacy of CDT. Silicon nanoparticles released from FCaO<jats:sub>2</jats:sub> are applied as in vitro fluorescent probes to image tumor cells overexpressing folate receptors. The results have presented that FZDF can actively accumulate in tumor cells, causing the mitochondrial membrane potential abnormality and a decrease in intracellular ATP content, thereby enhancing the self‐supplied CDT with less effect on normal cells and tissues. This work provides a novel strategy for constructing effective CDT nanosystems by hindering intracellular energy supply.","PeriodicalId":19903,"journal":{"name":"Particle & Particle Systems Characterization","volume":null,"pages":null},"PeriodicalIF":2.7000,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Particle & Particle Systems Characterization","FirstCategoryId":"88","ListUrlMain":"https://doi.org/10.1002/ppsc.202400068","RegionNum":4,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CHEMISTRY, PHYSICAL","Score":null,"Total":0}
引用次数: 0
Abstract
Chemodynamic therapy (CDT) has received increasing attention in recent years due to its effectiveness and specificity. However, the limited endogenous hydrogen peroxide (H2O2) concentration and resistance to reactive oxygen species in cancer cells hinder the further application of CDT. Here, an H2O2 self‐supplied nanosystem FCaO2@ZIF‐67‐2‐DG‐FA (FZDF) is synthesized to achieve efficient CDT improvement by Ca2+ overload and starvation therapy. Under folic acid‐mediated tumor targeting and endocytosis, the ZIF‐67 layer of FZDF is cleaved in the mildly acidic environment, releasing Co2+ and 2‐deoxy‐D‐glucose (2‐DG). The decomposition of exposed FCaO2 generates sufficient H2O2, which further produces abundant •OH via the Fenton‐like reaction of Co2+. Simultaneously, Ca2+ overload‐triggered mitochondrial dysfunction couples with glycolysis inhibition via 2‐DG‐induced starvation, which disrupts intracellular adenosine triphosphate (ATP) synthesis and amplifies the efficacy of CDT. Silicon nanoparticles released from FCaO2 are applied as in vitro fluorescent probes to image tumor cells overexpressing folate receptors. The results have presented that FZDF can actively accumulate in tumor cells, causing the mitochondrial membrane potential abnormality and a decrease in intracellular ATP content, thereby enhancing the self‐supplied CDT with less effect on normal cells and tissues. This work provides a novel strategy for constructing effective CDT nanosystems by hindering intracellular energy supply.
期刊介绍:
Particle & Particle Systems Characterization is an international, peer-reviewed, interdisciplinary journal focusing on all aspects of particle research. The journal joined the Advanced Materials family of journals in 2013. Particle has an impact factor of 4.194 (2018 Journal Impact Factor, Journal Citation Reports (Clarivate Analytics, 2019)).
Topics covered include the synthesis, characterization, and application of particles in a variety of systems and devices.
Particle covers nanotubes, fullerenes, micelles and alloy clusters, organic and inorganic materials, polymers, quantum dots, 2D materials, proteins, and other molecular biological systems.
Particle Systems include those in biomedicine, catalysis, energy-storage materials, environmental science, micro/nano-electromechanical systems, micro/nano-fluidics, molecular electronics, photonics, sensing, and others.
Characterization methods include microscopy, spectroscopy, electrochemical, diffraction, magnetic, and scattering techniques.