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- W3137109735 abstract "High levels of reactive oxygen species (ROS) in tumors have been shown to exert anti-tumor activity, leading to the concept of ROS induction as therapeutic strategy. The organometallic compound ferrocene (Fc) generates ROS through a reversible one-electron oxidation. Incorporation of Fc into a tumor-targeting, bioactive molecule can enhance its therapeutic activity and enable tumor specific delivery. Therefore, we conjugated Fc to five synthetic, Arg-Gly-Asp (RGD)-based integrin binding ligands to enable targeting of the cell adhesion and signaling receptor integrin subtypes αvβ3, α5β1, or αvβ6, which are overexpressed in various, distinct tumors. We designed and synthesized a library of integrin-ligand-ferrocene (ILF) derivatives and showed that ILF conjugates maintained the high integrin affinity and selectivity of their parent ligands. A thorough biological characterization allowed us to identify the two most promising ligands, an αvβ3 (L2b) and an αvβ6 (L3b) targeting ILF, which displayed selective integrin-dependent cell uptake and pronounced ferrocene-mediated anti-tumor effects in vitro, along with increased ROS production and DNA damage. Hence, ILFs are promising candidates for the selective, tumor-targeted delivery of ferrocene to maximize its anti-cancer efficacy and minimize systemic toxicity, thereby improving the therapeutic window of ferrocene compared to currently used non-selective anti-cancer drugs." @default.
- W3137109735 created "2021-03-29" @default.
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- W3137109735 date "2021-04-01" @default.
- W3137109735 modified "2023-10-14" @default.
- W3137109735 title "The organometallic ferrocene exhibits amplified anti-tumor activity by targeted delivery via highly selective ligands to αvβ3, αvβ6, or α5β1 integrins" @default.
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- W3137109735 doi "https://doi.org/10.1016/j.biomaterials.2021.120754" @default.
- W3137109735 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/33756215" @default.
- W3137109735 hasPublicationYear "2021" @default.
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