Nephrotoxicity Assessment with Human Kidney Tubuloids using Spherical Nucleic Acid-Based mRNA Nanoflares
Research output: Journal Publications and Reviews (RGC: 21, 22, 62) › 21_Publication in refereed journal › peer-review
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Detail(s)
Original language | English |
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Pages (from-to) | 5850–5858 |
Journal / Publication | Nano Letters |
Volume | 21 |
Issue number | 13 |
Online published | 22 Jun 2021 |
Publication status | Published - 14 Jul 2021 |
Link(s)
Abstract
Drug-induced nephrotoxicity represents an important cause of acute kidney injury with associated patient morbidity and mortality and is often responsible for termination of drug development, after extensive resource allocation. We have developed a human kidney tubuloid system that phenocopies, in 3D culture, kidney proximal tubules, a primary injury site of most nephrotoxicants. Traditional end point assays are often performed on 2D cultures of cells that have lost their differentiated phenotype. Herein, we pair a tubuloid system with Nanoflare (NF) mRNA nanosensors to achieve a facile, real-time assessment of drug nephrotoxicity. Using kidney injury molecule-1 (KIM-1) mRNA as a model injury biomarker, we verify NF specificity in engineered and adenovirus-transfected cells and confirm their efficacy to report tubular cell injury by aristolochic acid and cisplatin. The system also facilitates nephrotoxicity screening as demonstrated with 10 representative anticancer moieties. 5-Fluorouracil and paclitaxel induce acute tubular injury, as reflected by an NF signal increase.
Research Area(s)
- kidney organoids, spherical nucleic acid, nanoflare, clinical nephrotoxicity assessment, anticancer drugs, aristolochic acid, kidney injury molecule
Citation Format(s)
Nephrotoxicity Assessment with Human Kidney Tubuloids using Spherical Nucleic Acid-Based mRNA Nanoflares. / Wiraja, Christian; Mori, Yutaro; Ichimura, Takaharu; Hwang, Jangsun; Xu, Chenjie; Bonventre, Joseph V.
In: Nano Letters, Vol. 21, No. 13, 14.07.2021, p. 5850–5858.Research output: Journal Publications and Reviews (RGC: 21, 22, 62) › 21_Publication in refereed journal › peer-review