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 journalpeer-review

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Author(s)

  • Christian Wiraja
  • Yutaro Mori
  • Takaharu Ichimura
  • Jangsun Hwang
  • Joseph V. Bonventre

Related Research Unit(s)

Detail(s)

Original languageEnglish
Pages (from-to)5850–5858
Journal / PublicationNano Letters
Volume21
Issue number13
Online published22 Jun 2021
Publication statusPublished - 14 Jul 2021

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 journalpeer-review