{"title":"Copper-based metal–organic framework co-loaded doxorubicin and curcumin for anti-cancer with synergistic apoptosis and ferroptosis therapy","authors":"","doi":"10.1016/j.ijpharm.2024.124744","DOIUrl":null,"url":null,"abstract":"<div><div>The combination of chemotherapy and ferroptosis therapy can greatly improve the efficiency of tumor treatment. However, ferroptosis-based therapy is limited by the unsatisfactory Fenton activity and insufficient H<sub>2</sub>O<sub>2</sub> supply in tumor cells. In this work, a nano-drug delivery system Cur@DOX@MOF-199 NPs was constructed to combine ferroptosis and apoptosis by loading curcumin (Cur) and doxorubicin (DOX) based on the copper-based organic framework MOF-199. Cur@DOX@MOF-199 NPs decompose quickly by glutathione (GSH), releasing Cu<sup>2+</sup>, DOX and Cur. Cu<sup>2+</sup> can deplete GSH while also being reduced to Cu<sup>+</sup>; DOX can induce apoptosis and simultaneously boost H<sub>2</sub>O<sub>2</sub> production. Moreover, Cur enhanced the expression of intracellular heme oxygenase-1 (HO-1), for decomposing heme and releasing Fe<sup>2+</sup>, which further combined with Cu<sup>+</sup> to catalyze H<sub>2</sub>O<sub>2</sub> for hydroxyl radical (<sup><img></sup>OH) generation, leading to the accumulation of lipid peroxide and ferroptosis. As a result, Cur@DOX@MOF-199 NPs exhibited significantly enhanced antitumor efficacy in MCF-7 tumor-bearing mouse model, suggesting this nano formulation is an excellent synergetic pathway for apoptosis and ferroptosis.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":null,"pages":null},"PeriodicalIF":5.3000,"publicationDate":"2024-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"International Journal of Pharmaceutics","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0378517324009785","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
引用次数: 0
Abstract
The combination of chemotherapy and ferroptosis therapy can greatly improve the efficiency of tumor treatment. However, ferroptosis-based therapy is limited by the unsatisfactory Fenton activity and insufficient H2O2 supply in tumor cells. In this work, a nano-drug delivery system Cur@DOX@MOF-199 NPs was constructed to combine ferroptosis and apoptosis by loading curcumin (Cur) and doxorubicin (DOX) based on the copper-based organic framework MOF-199. Cur@DOX@MOF-199 NPs decompose quickly by glutathione (GSH), releasing Cu2+, DOX and Cur. Cu2+ can deplete GSH while also being reduced to Cu+; DOX can induce apoptosis and simultaneously boost H2O2 production. Moreover, Cur enhanced the expression of intracellular heme oxygenase-1 (HO-1), for decomposing heme and releasing Fe2+, which further combined with Cu+ to catalyze H2O2 for hydroxyl radical (OH) generation, leading to the accumulation of lipid peroxide and ferroptosis. As a result, Cur@DOX@MOF-199 NPs exhibited significantly enhanced antitumor efficacy in MCF-7 tumor-bearing mouse model, suggesting this nano formulation is an excellent synergetic pathway for apoptosis and ferroptosis.
期刊介绍:
The International Journal of Pharmaceutics is the third most cited journal in the "Pharmacy & Pharmacology" category out of 366 journals, being the true home for pharmaceutical scientists concerned with the physical, chemical and biological properties of devices and delivery systems for drugs, vaccines and biologicals, including their design, manufacture and evaluation. This includes evaluation of the properties of drugs, excipients such as surfactants and polymers and novel materials. The journal has special sections on pharmaceutical nanotechnology and personalized medicines, and publishes research papers, reviews, commentaries and letters to the editor as well as special issues.