{"title":"Fe<sup>3+</sup>-binding transferrin nanovesicles encapsulating sorafenib induce ferroptosis in hepatocellular carcinoma.","authors":"Youmei Xiao, Zhanxue Xu, Yuan Cheng, Rufan Huang, Yuan Xie, Hsiang-I Tsai, Hualian Zha, Lifang Xi, Kai Wang, Xiaoli Cheng, Yanfeng Gao, Changhua Zhang, Fang Cheng, Hongbo Chen","doi":"10.1186/s40824-023-00401-x","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Ferroptosis, iron-dependent cell death, is an established mechanism for cancer suppression, particularly in hepatocellular carcinoma (HCC). Sorafenib (SOR), a frontline drug for the treatment of HCC, induces ferroptosis by inhibiting the Solute Carrier family 7 member 11 (SLC7A11), with inadequate ferroptosis notably contributing to SOR resistance in tumor cells.</p><p><strong>Methods: </strong>To further verify the biological targets associated with ferroptosis in HCC, an analysis of the Cancer Genome Atlas (TCGA) database was performed to find a significant co-upregulation of SLC7A11 and transferrin receptor (TFRC), Herein, cell membrane-derived transferrin nanovesicles (TF NVs) coupled with Fe<sup>3+</sup> and encapsulated SOR (SOR@TF-Fe<sup>3+</sup> NVs) were established to synergistically promote ferroptosis, which promoted the iron transport metabolism by TFRC/TF-Fe<sup>3+</sup> and enhanced SOR efficacy by inhibiting the SLC7A11.</p><p><strong>Results: </strong>In vivo and in vitro experiments revealed that SOR@TF-Fe<sup>3+</sup> NVs predominantly accumulate in the liver, and specifically targeted HCC cells overexpressing TFRC. Various tests demonstrated SOR@TF-Fe<sup>3+</sup> NVs accelerated Fe<sup>3+</sup> absorption and transformation in HCC cells. Importantly, SOR@TF-Fe<sup>3+</sup> NVs were more effective in promoting the accumulation of lipid peroxides (LPO), inhibiting tumor proliferation, and prolonging survival rates in HCC mouse model than SOR and TF- Fe<sup>3+</sup> NVs alone.</p><p><strong>Conclusions: </strong>The present work provides a promising therapeutic strategy for the targeted treatment of HCC.</p>","PeriodicalId":9079,"journal":{"name":"Biomaterials Research","volume":null,"pages":null},"PeriodicalIF":11.3000,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10314404/pdf/","citationCount":"2","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biomaterials Research","FirstCategoryId":"5","ListUrlMain":"https://doi.org/10.1186/s40824-023-00401-x","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"Medicine","Score":null,"Total":0}
引用次数: 2
Abstract
Background: Ferroptosis, iron-dependent cell death, is an established mechanism for cancer suppression, particularly in hepatocellular carcinoma (HCC). Sorafenib (SOR), a frontline drug for the treatment of HCC, induces ferroptosis by inhibiting the Solute Carrier family 7 member 11 (SLC7A11), with inadequate ferroptosis notably contributing to SOR resistance in tumor cells.
Methods: To further verify the biological targets associated with ferroptosis in HCC, an analysis of the Cancer Genome Atlas (TCGA) database was performed to find a significant co-upregulation of SLC7A11 and transferrin receptor (TFRC), Herein, cell membrane-derived transferrin nanovesicles (TF NVs) coupled with Fe3+ and encapsulated SOR (SOR@TF-Fe3+ NVs) were established to synergistically promote ferroptosis, which promoted the iron transport metabolism by TFRC/TF-Fe3+ and enhanced SOR efficacy by inhibiting the SLC7A11.
Results: In vivo and in vitro experiments revealed that SOR@TF-Fe3+ NVs predominantly accumulate in the liver, and specifically targeted HCC cells overexpressing TFRC. Various tests demonstrated SOR@TF-Fe3+ NVs accelerated Fe3+ absorption and transformation in HCC cells. Importantly, SOR@TF-Fe3+ NVs were more effective in promoting the accumulation of lipid peroxides (LPO), inhibiting tumor proliferation, and prolonging survival rates in HCC mouse model than SOR and TF- Fe3+ NVs alone.
Conclusions: The present work provides a promising therapeutic strategy for the targeted treatment of HCC.
期刊介绍:
Biomaterials Research, the official journal of the Korean Society for Biomaterials, is an open-access interdisciplinary publication that focuses on all aspects of biomaterials research. The journal covers a wide range of topics including novel biomaterials, advanced techniques for biomaterial synthesis and fabrication, and their application in biomedical fields. Specific areas of interest include functional biomaterials, drug and gene delivery systems, tissue engineering, nanomedicine, nano/micro-biotechnology, bio-imaging, regenerative medicine, medical devices, 3D printing, and stem cell research. By exploring these research areas, Biomaterials Research aims to provide valuable insights and promote advancements in the biomaterials field.