{"title":"A manganese-oxide nano-rambutan as the intrinsic modifier for hypericin delivery and triple-negative breast cancer treatment","authors":"","doi":"10.1016/j.ijpharm.2024.124824","DOIUrl":null,"url":null,"abstract":"<div><div>The anti-tumor efficacy of naturally derived photosensitizer-hypericin (Hy) is dampened by hypoxia and over-expressed glutathione in the tumor microenvironment (TME). For rewiring the TME, we encapsulated Hy to an intrinsic modifier-manganese oxide-formed nanorambutan (MnO<sub>x</sub>-Hy NR). In triple-negative breast cancer cells, MnO<sub>x</sub>-Hy NR not only consumed glutathione through Mn<sup>2+</sup> and hypericin release but also facilitated O<sub>2</sub> production to relieve hypoxia, through which the reactive oxygen species (ROS) generation was strengthened by endoplasmic reticulum targeting hypericin. In the meantime, glutathione consumption-induced glutathione peroxidase 4 (GPX4) inactivation and the elevation of lipid hydroperoxide (LPO) level further triggered ferroptosis. Then, the combination of PDT and ferroptosis contributed to a synergic immunogenic cell death (ICD) effect in 4 T1 cells, facilitating the adaptive anti-tumor immune response activation. Thereby, MnO<sub>x</sub>-Hy NR exhibited excellent anti-tumor effects both in primary and distant tumors through the abscopal effect, as well as significant lung metastasis inhibition in the 4 T1 mouse metastatic tumor model.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":null,"pages":null},"PeriodicalIF":5.3000,"publicationDate":"2024-10-11","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/S0378517324010585","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 anti-tumor efficacy of naturally derived photosensitizer-hypericin (Hy) is dampened by hypoxia and over-expressed glutathione in the tumor microenvironment (TME). For rewiring the TME, we encapsulated Hy to an intrinsic modifier-manganese oxide-formed nanorambutan (MnOx-Hy NR). In triple-negative breast cancer cells, MnOx-Hy NR not only consumed glutathione through Mn2+ and hypericin release but also facilitated O2 production to relieve hypoxia, through which the reactive oxygen species (ROS) generation was strengthened by endoplasmic reticulum targeting hypericin. In the meantime, glutathione consumption-induced glutathione peroxidase 4 (GPX4) inactivation and the elevation of lipid hydroperoxide (LPO) level further triggered ferroptosis. Then, the combination of PDT and ferroptosis contributed to a synergic immunogenic cell death (ICD) effect in 4 T1 cells, facilitating the adaptive anti-tumor immune response activation. Thereby, MnOx-Hy NR exhibited excellent anti-tumor effects both in primary and distant tumors through the abscopal effect, as well as significant lung metastasis inhibition in the 4 T1 mouse metastatic tumor model.
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.