Pengfei Yang , Jie Zhang , Yi Chang , Lingxue Tang , Guanglei Ma , Xinhe Liu , Fangli Gao , Xiaoming Ma , Yuming Guo
{"title":"肿瘤微环境响应智能纳米平台,通过协同增强谷胱甘肽耗竭和缺氧缓解协同肿瘤治疗","authors":"Pengfei Yang , Jie Zhang , Yi Chang , Lingxue Tang , Guanglei Ma , Xinhe Liu , Fangli Gao , Xiaoming Ma , Yuming Guo","doi":"10.1016/j.jinorgbio.2025.113005","DOIUrl":null,"url":null,"abstract":"<div><div>As innovative therapeutic strategy, chemodynamic therapy (CDT) and photodynamic therapy (PDT) show great promise for tumor therapy. However, their therapeutic efficacy is seriously limited by the hypoxia and insufficient H<sub>2</sub>O<sub>2</sub> supply of the tumor microenvironment. Juglone (JUG), a naturally-occurring naphthoquinone, can increase the intracellular H<sub>2</sub>O<sub>2</sub> concentration and serve as an inhibitor of peptidyl-prolyl cis-trans isomerase NIMA-interacting 1. Herein, a nanoplatform composed of Fe-based metal-organic framework core, MnO<sub>2</sub> layer, JUG payload, and hyaluronic acid (HA) decoration (Fe-TCPP@MnO<sub>2</sub>@JUG@HA) was designed and prepared. The MnO<sub>2</sub> layer can prevent the phototoxicity of tetrakis (4-carboxyphenyl)porphyrin (TCPP) during transportation and catalyze H<sub>2</sub>O<sub>2</sub> to produce O<sub>2</sub> to enhance the PDT efficacy. HA can improve the delivery efficiency to tumor. Then Fe<sup>3+</sup> was reduced to Fe<sup>2+</sup> and MnO<sub>2</sub> was reduced to Mn<sup>2+</sup> because of the weak acidity and high concentration glutathione (GSH), causing the nanoplatform collapse, TCPP activation, and JUG release. GSH-depletion reduce the reactive oxygen species (ROS) scavenging effect and further enhance the PDT efficacy, inhibited the biosynthesis of lipid repair enzyme glutathione peroxidase 4 and promoted the ferroptosis efficiency by destroying redox balance. This PDT/CDT/chemotherapy triple synergistic apoptosis-ferroptosis strategy exhibited good tumor therapeutic efficacy and excellent biocompatibility, implying the promising future for efficient tumor treatment.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"272 ","pages":"Article 113005"},"PeriodicalIF":3.2000,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Tumor microenvironment responsive smart nanoplatform for synergistic tumor therapy through co-enhancement of GSH depletion and hypoxia relief\",\"authors\":\"Pengfei Yang , Jie Zhang , Yi Chang , Lingxue Tang , Guanglei Ma , Xinhe Liu , Fangli Gao , Xiaoming Ma , Yuming Guo\",\"doi\":\"10.1016/j.jinorgbio.2025.113005\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>As innovative therapeutic strategy, chemodynamic therapy (CDT) and photodynamic therapy (PDT) show great promise for tumor therapy. However, their therapeutic efficacy is seriously limited by the hypoxia and insufficient H<sub>2</sub>O<sub>2</sub> supply of the tumor microenvironment. Juglone (JUG), a naturally-occurring naphthoquinone, can increase the intracellular H<sub>2</sub>O<sub>2</sub> concentration and serve as an inhibitor of peptidyl-prolyl cis-trans isomerase NIMA-interacting 1. Herein, a nanoplatform composed of Fe-based metal-organic framework core, MnO<sub>2</sub> layer, JUG payload, and hyaluronic acid (HA) decoration (Fe-TCPP@MnO<sub>2</sub>@JUG@HA) was designed and prepared. The MnO<sub>2</sub> layer can prevent the phototoxicity of tetrakis (4-carboxyphenyl)porphyrin (TCPP) during transportation and catalyze H<sub>2</sub>O<sub>2</sub> to produce O<sub>2</sub> to enhance the PDT efficacy. HA can improve the delivery efficiency to tumor. Then Fe<sup>3+</sup> was reduced to Fe<sup>2+</sup> and MnO<sub>2</sub> was reduced to Mn<sup>2+</sup> because of the weak acidity and high concentration glutathione (GSH), causing the nanoplatform collapse, TCPP activation, and JUG release. GSH-depletion reduce the reactive oxygen species (ROS) scavenging effect and further enhance the PDT efficacy, inhibited the biosynthesis of lipid repair enzyme glutathione peroxidase 4 and promoted the ferroptosis efficiency by destroying redox balance. This PDT/CDT/chemotherapy triple synergistic apoptosis-ferroptosis strategy exhibited good tumor therapeutic efficacy and excellent biocompatibility, implying the promising future for efficient tumor treatment.</div></div>\",\"PeriodicalId\":364,\"journal\":{\"name\":\"Journal of Inorganic Biochemistry\",\"volume\":\"272 \",\"pages\":\"Article 113005\"},\"PeriodicalIF\":3.2000,\"publicationDate\":\"2025-07-11\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Inorganic Biochemistry\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0162013425001850\",\"RegionNum\":2,\"RegionCategory\":\"化学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Inorganic Biochemistry","FirstCategoryId":"99","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0162013425001850","RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
Tumor microenvironment responsive smart nanoplatform for synergistic tumor therapy through co-enhancement of GSH depletion and hypoxia relief
As innovative therapeutic strategy, chemodynamic therapy (CDT) and photodynamic therapy (PDT) show great promise for tumor therapy. However, their therapeutic efficacy is seriously limited by the hypoxia and insufficient H2O2 supply of the tumor microenvironment. Juglone (JUG), a naturally-occurring naphthoquinone, can increase the intracellular H2O2 concentration and serve as an inhibitor of peptidyl-prolyl cis-trans isomerase NIMA-interacting 1. Herein, a nanoplatform composed of Fe-based metal-organic framework core, MnO2 layer, JUG payload, and hyaluronic acid (HA) decoration (Fe-TCPP@MnO2@JUG@HA) was designed and prepared. The MnO2 layer can prevent the phototoxicity of tetrakis (4-carboxyphenyl)porphyrin (TCPP) during transportation and catalyze H2O2 to produce O2 to enhance the PDT efficacy. HA can improve the delivery efficiency to tumor. Then Fe3+ was reduced to Fe2+ and MnO2 was reduced to Mn2+ because of the weak acidity and high concentration glutathione (GSH), causing the nanoplatform collapse, TCPP activation, and JUG release. GSH-depletion reduce the reactive oxygen species (ROS) scavenging effect and further enhance the PDT efficacy, inhibited the biosynthesis of lipid repair enzyme glutathione peroxidase 4 and promoted the ferroptosis efficiency by destroying redox balance. This PDT/CDT/chemotherapy triple synergistic apoptosis-ferroptosis strategy exhibited good tumor therapeutic efficacy and excellent biocompatibility, implying the promising future for efficient tumor treatment.
期刊介绍:
The Journal of Inorganic Biochemistry is an established international forum for research in all aspects of Biological Inorganic Chemistry. Original papers of a high scientific level are published in the form of Articles (full length papers), Short Communications, Focused Reviews and Bioinorganic Methods. Topics include: the chemistry, structure and function of metalloenzymes; the interaction of inorganic ions and molecules with proteins and nucleic acids; the synthesis and properties of coordination complexes of biological interest including both structural and functional model systems; the function of metal- containing systems in the regulation of gene expression; the role of metals in medicine; the application of spectroscopic methods to determine the structure of metallobiomolecules; the preparation and characterization of metal-based biomaterials; and related systems. The emphasis of the Journal is on the structure and mechanism of action of metallobiomolecules.