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Co-Delivery of Renal Clearable Cerium Complex and Synergistic Antioxidant Iron Complex for Treating Sepsis

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Title
Co-Delivery of Renal Clearable Cerium Complex and Synergistic Antioxidant Iron Complex for Treating Sepsis
Author(s)
Young Geon Kim; Boomin Choi; Yunjung Lee; Lee, Bohyung; Kim, Hyunmin; Choi, Seung Hong; Park, Ok Kyu; Yubeen Kim; Seungmin Baik; Kim, Dokyoon; Min Soh; Kim, Chi Kyung; Taeghwan Hyeon
Publication Date
2024-10
Journal
ACS Nano, v.18, no.43, pp.29535 - 29549
Publisher
American Chemical Society
Abstract
The mononuclear phagocytic system clears the circulating inorganic nanomaterials from the bloodstream, which raises concerns about the chronic toxicity of the accumulated metal species. A better understanding of the behavior of each metal after systemic injection is thus required for clinical translations. This study investigates the significance of the metal-ligand interaction on the accumulation of cerium and demonstrates that only the form in which cerium is coordinated to a multidentate chelator with a strong binding affinity does not accumulate in major organs. Specifically, cerium complexed with diethylenetriamine pentaacetic acid (DTPA) forms renally excretable nanoparticles in vivo to circumvent the leaching of cerium ions, whereas weakly coordinated cerium-based nanomaterials produce insoluble precipitates upon encountering physiological phosphate anions. Ceria-based renally clearable nanoparticles (CRNs) derived from cerium-DTPA are utilized as the antioxidant pair with iron-DTPA, in which their combination leverages the Fenton reaction to synergistically scavenge hydrogen peroxide. This reduces the gene expression of pro-inflammatory factors in the macrophages activated with lipopolysaccharide as well as improves the survival rate of septic mice by alleviating the systemic inflammatory response and its downstream tissue injury in the liver, spleen, and kidneys. This study demonstrates that CRNs combined with iron-DTPA can be utilized as nonaccumulative nanomedicines for treating systemic inflammation, thereby overcoming the limitations of conventional ceria nanoparticle-based treatments.
URI
https://pr.ibs.re.kr/handle/8788114/15589
DOI
10.1021/acsnano.4c05902
ISSN
1936-0851
Appears in Collections:
Center for Nanoparticle Research(나노입자 연구단) > 1. Journal Papers (저널논문)
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