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ACS Nano, Oct 17 2024, | https://doi.org/10.1021/acsnano.4c05902 Co-Delivery of Renal Clearable Cerium Complex and Synergistic Antioxidant Iron Complex for Treating Sepsis

Young Geon Kim ^1,2∇, Boomin Choi ^1,3∇, Yunjung Lee^1,2∇, Bohyung Lee ⁴, Hyunmin Kim ⁴, Seung Hong Choi ⁵, Ok Kyu Park ⁵, Yubeen Kim ^1,2, Seungmin Baik ^1,2, Dokyoon Kim ⁶, Min Soh ^1,3*, Chi Kyung Kim ^4*, Taeghwan Hyeon ^1,2*

¹Center for Nanoparticle Research, Institute for Basic Science (IBS), Seoul 08826, Republic of Korea.

²School of Chemical and Biological Engineering, and Institute of Chemical Processes, Seoul National University, Seoul 08826, Republic of Korea.

³Center for Advanced Pharmaceutical Technology, HyeonTechNBio Inc., Seoul 08826, Republic of Korea.

⁴Department of Neurology, Korea University Guro Hospital, Korea University College of Medicine, Seoul 08308, Republic of Korea.

⁵Department of Radiology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul 03080, Republic of Korea.

⁶Department of Bionano Engineering, Hanyang University, Ansan 15588, Republic of Korea.

^∇Y.G.K., B.C., and Y.L. contributed equally to this work.

*Corresponding Authors : Min Soh, Chi Kyung Kim, Taeghwan Hyeon

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.

논문정보

형식Research article
게재일2024년 10월 (BRIC 등록일 2024-10-18)
연구진국내 연구진
분야 바이오·의료융합 > 바이오센싱 및 나노바이오물질

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