Nanoparticle-Enhanced RT-QuIC (Nano-QuIC) Diagnostic Assay for Misfolded Proteins

Peter R. Christenson; Manci Li; Gage Rowden; Peter A. Larsen; Sang Hyun Oh

doi:10.1021/acs.nanolett.3c01001

Nanoparticle-Enhanced RT-QuIC (Nano-QuIC) Diagnostic Assay for Misfolded Proteins

Peter R. Christenson, Manci Li, Gage Rowden, Peter A. Larsen, Sang Hyun Oh

Research output: Contribution to journal › Article › peer-review

1 Scopus citations

Abstract

Misfolded proteins associated with various neurodegenerative diseases often accumulate in tissues or circulate in biological fluids years before the clinical onset, thus representing ideal diagnostic targets. Real-time quaking-induced conversion (RT-QuIC), a protein-based seeded-amplification assay, holds great potential for early disease detection, yet challenges remain for routine diagnostic application. Chronic Wasting Disease (CWD), associated with misfolded prion proteins of cervids, serves as an ideal model for evaluating new RT-QuIC methodologies. In this study, we investigate the previously untested hypothesis that incorporating nanoparticles into RT-QuIC assays can enhance their speed and sensitivity when applied to biological samples. We show that adding 50 nm silica nanoparticles to RT-QuIC experiments (termed Nano-QuIC) for CWD diagnostics greatly improves the performance by reducing detection times 2.5-fold and increasing sensitivity 10-fold by overcoming the effect of inhibitors in complex tissue samples. Crucially, no false positives were observed with these 50 nm silica nanoparticles, demonstrating the enhanced reliability and potential for diagnostic application of Nano-QuIC in detecting misfolded proteins.

Original language	English (US)
Pages (from-to)	4074-4081
Number of pages	8
Journal	Nano letters
Volume	23
Issue number	9
DOIs	https://doi.org/10.1021/acs.nanolett.3c01001
State	Published - May 10 2023

Bibliographical note

Funding Information:
Funding for research performed herein was provided by the Minnesota State Legislature through the Minnesota Legislative-Citizen Commission on Minnesota Resources (LCCMR) and Minnesota Agricultural Experiment Station Rapid Agricultural Response Fund to P.R.C., M.C., G.R., P.A.L., and S.-H.O., the Sanford P. Bordeau Chair in Electrical Engineering at the University of Minnesota and the McKnight Foundation to S.-H.O., and start-up funds awarded to P.A.L. through the Minnesota Agricultural, Research, Education, Extension and Technology Transfer (AGREETT) program. Portions of this work were conducted in the Minnesota Nano Center, which is supported by the National Science Foundation (NSF) through the National Nano Coordinated Infrastructure Network (NNCI) under Award ECCS-2025124. Portions of this work were carried out in the University of Minnesota Characterization Facility, which receives partial support from the NSF through the MRSEC (Award DMR-2011401) program.

Publisher Copyright:
© 2023 American Chemical Society.

Keywords

RT-QuIC
amyloid
gold nanoparticle
prions
protein misfolding
silica nanoparticle

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title = "Nanoparticle-Enhanced RT-QuIC (Nano-QuIC) Diagnostic Assay for Misfolded Proteins",

abstract = "Misfolded proteins associated with various neurodegenerative diseases often accumulate in tissues or circulate in biological fluids years before the clinical onset, thus representing ideal diagnostic targets. Real-time quaking-induced conversion (RT-QuIC), a protein-based seeded-amplification assay, holds great potential for early disease detection, yet challenges remain for routine diagnostic application. Chronic Wasting Disease (CWD), associated with misfolded prion proteins of cervids, serves as an ideal model for evaluating new RT-QuIC methodologies. In this study, we investigate the previously untested hypothesis that incorporating nanoparticles into RT-QuIC assays can enhance their speed and sensitivity when applied to biological samples. We show that adding 50 nm silica nanoparticles to RT-QuIC experiments (termed Nano-QuIC) for CWD diagnostics greatly improves the performance by reducing detection times 2.5-fold and increasing sensitivity 10-fold by overcoming the effect of inhibitors in complex tissue samples. Crucially, no false positives were observed with these 50 nm silica nanoparticles, demonstrating the enhanced reliability and potential for diagnostic application of Nano-QuIC in detecting misfolded proteins.",

keywords = "RT-QuIC, amyloid, gold nanoparticle, prions, protein misfolding, silica nanoparticle",

author = "Christenson, {Peter R.} and Manci Li and Gage Rowden and Larsen, {Peter A.} and Oh, {Sang Hyun}",

note = "Funding Information: Funding for research performed herein was provided by the Minnesota State Legislature through the Minnesota Legislative-Citizen Commission on Minnesota Resources (LCCMR) and Minnesota Agricultural Experiment Station Rapid Agricultural Response Fund to P.R.C., M.C., G.R., P.A.L., and S.-H.O., the Sanford P. Bordeau Chair in Electrical Engineering at the University of Minnesota and the McKnight Foundation to S.-H.O., and start-up funds awarded to P.A.L. through the Minnesota Agricultural, Research, Education, Extension and Technology Transfer (AGREETT) program. Portions of this work were conducted in the Minnesota Nano Center, which is supported by the National Science Foundation (NSF) through the National Nano Coordinated Infrastructure Network (NNCI) under Award ECCS-2025124. Portions of this work were carried out in the University of Minnesota Characterization Facility, which receives partial support from the NSF through the MRSEC (Award DMR-2011401) program. Publisher Copyright: {\textcopyright} 2023 American Chemical Society.",

year = "2023",

month = may,

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doi = "10.1021/acs.nanolett.3c01001",

language = "English (US)",

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AU - Li, Manci

AU - Rowden, Gage

AU - Larsen, Peter A.

AU - Oh, Sang Hyun

N1 - Funding Information: Funding for research performed herein was provided by the Minnesota State Legislature through the Minnesota Legislative-Citizen Commission on Minnesota Resources (LCCMR) and Minnesota Agricultural Experiment Station Rapid Agricultural Response Fund to P.R.C., M.C., G.R., P.A.L., and S.-H.O., the Sanford P. Bordeau Chair in Electrical Engineering at the University of Minnesota and the McKnight Foundation to S.-H.O., and start-up funds awarded to P.A.L. through the Minnesota Agricultural, Research, Education, Extension and Technology Transfer (AGREETT) program. Portions of this work were conducted in the Minnesota Nano Center, which is supported by the National Science Foundation (NSF) through the National Nano Coordinated Infrastructure Network (NNCI) under Award ECCS-2025124. Portions of this work were carried out in the University of Minnesota Characterization Facility, which receives partial support from the NSF through the MRSEC (Award DMR-2011401) program. Publisher Copyright: © 2023 American Chemical Society.

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N2 - Misfolded proteins associated with various neurodegenerative diseases often accumulate in tissues or circulate in biological fluids years before the clinical onset, thus representing ideal diagnostic targets. Real-time quaking-induced conversion (RT-QuIC), a protein-based seeded-amplification assay, holds great potential for early disease detection, yet challenges remain for routine diagnostic application. Chronic Wasting Disease (CWD), associated with misfolded prion proteins of cervids, serves as an ideal model for evaluating new RT-QuIC methodologies. In this study, we investigate the previously untested hypothesis that incorporating nanoparticles into RT-QuIC assays can enhance their speed and sensitivity when applied to biological samples. We show that adding 50 nm silica nanoparticles to RT-QuIC experiments (termed Nano-QuIC) for CWD diagnostics greatly improves the performance by reducing detection times 2.5-fold and increasing sensitivity 10-fold by overcoming the effect of inhibitors in complex tissue samples. Crucially, no false positives were observed with these 50 nm silica nanoparticles, demonstrating the enhanced reliability and potential for diagnostic application of Nano-QuIC in detecting misfolded proteins.

AB - Misfolded proteins associated with various neurodegenerative diseases often accumulate in tissues or circulate in biological fluids years before the clinical onset, thus representing ideal diagnostic targets. Real-time quaking-induced conversion (RT-QuIC), a protein-based seeded-amplification assay, holds great potential for early disease detection, yet challenges remain for routine diagnostic application. Chronic Wasting Disease (CWD), associated with misfolded prion proteins of cervids, serves as an ideal model for evaluating new RT-QuIC methodologies. In this study, we investigate the previously untested hypothesis that incorporating nanoparticles into RT-QuIC assays can enhance their speed and sensitivity when applied to biological samples. We show that adding 50 nm silica nanoparticles to RT-QuIC experiments (termed Nano-QuIC) for CWD diagnostics greatly improves the performance by reducing detection times 2.5-fold and increasing sensitivity 10-fold by overcoming the effect of inhibitors in complex tissue samples. Crucially, no false positives were observed with these 50 nm silica nanoparticles, demonstrating the enhanced reliability and potential for diagnostic application of Nano-QuIC in detecting misfolded proteins.

KW - RT-QuIC

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KW - gold nanoparticle

KW - prions

KW - protein misfolding

KW - silica nanoparticle

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SN - 1530-6984

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JO - Nano letters

JF - Nano letters

IS - 9

ER -

Nanoparticle-Enhanced RT-QuIC (Nano-QuIC) Diagnostic Assay for Misfolded Proteins

Abstract

Bibliographical note

Keywords

MRSEC Support

PubMed: MeSH publication types

Publisher link

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University of Minnesota Materials Research Science and Engineering Center (DMR-2011401)

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