Optical Nanosensor for Intracellular and Intracranial Detection of Amyloid-Beta

Merav Antman-Passig; Eitan Wong; Georgia R. Frost; Christian Cupo; Janki Shah; Albert Agustinus; Ziyu Chen; Chiara Mancinelli; Maikel Kamel; Thomas Li; Lauren A. Jonas; Yue Ming Li; Daniel A. Heller

doi:10.1021/acsnano.2c00054

Optical Nanosensor for Intracellular and Intracranial Detection of Amyloid-Beta

Merav Antman-Passig, Eitan Wong, Georgia R. Frost, Christian Cupo, Janki Shah, Albert Agustinus, Ziyu Chen, Chiara Mancinelli, Maikel Kamel, Thomas Li, Lauren A. Jonas, Yue Ming Li, Daniel A. Heller

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

22 Scopus citations

Abstract

Amyloid-beta (Aβ) deposition occurs in the early stages of Alzheimer’s disease (AD), but the early detection of Aβ is a persistent challenge. Herein, we engineered a near-infrared optical nanosensor capable of detecting Aβ intracellularly in live cells and intracranially in vivo. The sensor is composed of single-walled carbon nanotubes functionalized with Aβ wherein Aβ-Aβ interactions drive the response. We found that the Aβ nanosensors selectively responded to Aβ via solvatochromic modulation of the near-infrared emission of the nanotube. The sensor tracked Aβ accumulation in live cells and, upon intracranial administration in a genetic model of AD, signaled distinct responses in aged mice. This technology enables the interrogation of molecular mechanisms underlying Aβ neurotoxicity in the development of AD in living systems.

Original language	English
Pages (from-to)	7269-7283
Number of pages	15
Journal	ACS Nano
Volume	16
Issue number	5
DOIs	https://doi.org/10.1021/acsnano.2c00054
State	Published - 24 May 2022
Externally published	Yes

Bibliographical note

Publisher Copyright:
© 2022 American Chemical Society.

Funding

This work was supported in part by the NCI and Cancer Center Support Grant P30-CA008748, NINDS (R01-NS116353), NIA (R01AG061350), the National Science Foundation CAREER Award (1752506), the JPB Foundation (MR-2020-2155), the Ara Parseghian Medical Research Fund, the American Cancer Society Research Scholar Grant (GC230452), the Pershing Square Sohn Cancer Research Alliance, the Honorable Tina Brozman Foundation for Ovarian Cancer Research, the Expect Miracles Foundation - Financial Services Against Cancer, the Anna Fuller Fund, the Louis and Rachel Rudin Foundation, Emerson Collective, MSK’s Cycle for Survival’s Equinox Innovation Award in Rare Cancers, the Alan and Sandra Gerry Metastasis Research Initiative, Mr. William H. Goodwin and Mrs. Alice Goodwin and the Commonwealth Foundation for Cancer Research, and the Experimental Therapeutics Center of Memorial Sloan Kettering Cancer Center. M.A.P. was supported by the Joe W. and Dorothy Dorsett Brown Foundation. A.A. was supported by the PhRMA Foundation Predoctoral Fellowship.

Funders	Funder number
Alan and Sandra Gerry Metastasis Research Initiative
Anna Fuller Fund
Commonwealth Foundation for Cancer Research
Expect Miracles Foundation
National Science Foundation	1752506
American Cancer Society	GC230452
National Institute on Aging	R01AG061350
National Cancer Institute	P30CA008748
National Institute of Neurological Disorders and Stroke	R01-NS116353
Joe W. and Dorothy Dorsett Brown Foundation
Pharmaceutical Research and Manufacturers of America Foundation
Honorable Tina Brozman Foundation
JPB Foundation	MR-2020-2155
Pershing Square Sohn Cancer Research Alliance
Ara Parseghian Medical Research Fund

Keywords

biosensor
carbon nanomaterials
fluorescence
nanocarbon
neurodegenerative disease

Access to Document

10.1021/acsnano.2c00054

Cite this

@article{350f2cbf7dbe486a86c4ec3f97512b28,

title = "Optical Nanosensor for Intracellular and Intracranial Detection of Amyloid-Beta",

abstract = "Amyloid-beta (Aβ) deposition occurs in the early stages of Alzheimer{\textquoteright}s disease (AD), but the early detection of Aβ is a persistent challenge. Herein, we engineered a near-infrared optical nanosensor capable of detecting Aβ intracellularly in live cells and intracranially in vivo. The sensor is composed of single-walled carbon nanotubes functionalized with Aβ wherein Aβ-Aβ interactions drive the response. We found that the Aβ nanosensors selectively responded to Aβ via solvatochromic modulation of the near-infrared emission of the nanotube. The sensor tracked Aβ accumulation in live cells and, upon intracranial administration in a genetic model of AD, signaled distinct responses in aged mice. This technology enables the interrogation of molecular mechanisms underlying Aβ neurotoxicity in the development of AD in living systems.",

keywords = "biosensor, carbon nanomaterials, fluorescence, nanocarbon, neurodegenerative disease",

author = "Merav Antman-Passig and Eitan Wong and Frost, {Georgia R.} and Christian Cupo and Janki Shah and Albert Agustinus and Ziyu Chen and Chiara Mancinelli and Maikel Kamel and Thomas Li and Jonas, {Lauren A.} and Li, {Yue Ming} and Heller, {Daniel A.}",

note = "Publisher Copyright: {\textcopyright} 2022 American Chemical Society.",

year = "2022",

month = may,

day = "24",

doi = "10.1021/acsnano.2c00054",

language = "אנגלית",

volume = "16",

pages = "7269--7283",

journal = "ACS Nano",

issn = "1936-0851",

publisher = "American Chemical Society",

number = "5",

}

TY - JOUR

T1 - Optical Nanosensor for Intracellular and Intracranial Detection of Amyloid-Beta

AU - Antman-Passig, Merav

AU - Wong, Eitan

AU - Frost, Georgia R.

AU - Cupo, Christian

AU - Shah, Janki

AU - Agustinus, Albert

AU - Chen, Ziyu

AU - Mancinelli, Chiara

AU - Kamel, Maikel

AU - Li, Thomas

AU - Jonas, Lauren A.

AU - Li, Yue Ming

AU - Heller, Daniel A.

PY - 2022/5/24

Y1 - 2022/5/24

N2 - Amyloid-beta (Aβ) deposition occurs in the early stages of Alzheimer’s disease (AD), but the early detection of Aβ is a persistent challenge. Herein, we engineered a near-infrared optical nanosensor capable of detecting Aβ intracellularly in live cells and intracranially in vivo. The sensor is composed of single-walled carbon nanotubes functionalized with Aβ wherein Aβ-Aβ interactions drive the response. We found that the Aβ nanosensors selectively responded to Aβ via solvatochromic modulation of the near-infrared emission of the nanotube. The sensor tracked Aβ accumulation in live cells and, upon intracranial administration in a genetic model of AD, signaled distinct responses in aged mice. This technology enables the interrogation of molecular mechanisms underlying Aβ neurotoxicity in the development of AD in living systems.

AB - Amyloid-beta (Aβ) deposition occurs in the early stages of Alzheimer’s disease (AD), but the early detection of Aβ is a persistent challenge. Herein, we engineered a near-infrared optical nanosensor capable of detecting Aβ intracellularly in live cells and intracranially in vivo. The sensor is composed of single-walled carbon nanotubes functionalized with Aβ wherein Aβ-Aβ interactions drive the response. We found that the Aβ nanosensors selectively responded to Aβ via solvatochromic modulation of the near-infrared emission of the nanotube. The sensor tracked Aβ accumulation in live cells and, upon intracranial administration in a genetic model of AD, signaled distinct responses in aged mice. This technology enables the interrogation of molecular mechanisms underlying Aβ neurotoxicity in the development of AD in living systems.

KW - biosensor

KW - carbon nanomaterials

KW - fluorescence

KW - nanocarbon

KW - neurodegenerative disease

UR - http://www.scopus.com/inward/record.url?scp=85129078106&partnerID=8YFLogxK

U2 - 10.1021/acsnano.2c00054

DO - 10.1021/acsnano.2c00054

M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???

C2 - 35420796

AN - SCOPUS:85129078106

SN - 1936-0851

VL - 16

SP - 7269

EP - 7283

JO - ACS Nano

JF - ACS Nano

IS - 5

ER -

Optical Nanosensor for Intracellular and Intracranial Detection of Amyloid-Beta

Abstract

Bibliographical note

Funding

Keywords

Access to Document

Other files and links

Fingerprint

Cite this