Cited by 125Luminescence and Fluorescent MaterialsNanoplatforms for cancer theranosticsCalcium signaling and nucleotide metabolism

A Carbon Nanotube Optical Reporter Maps Endolysosomal Lipid Flux

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Jena, Prakrit V., Roxbury, Daniel, Galassi, Thomas V., Akkari, Leila, Horoszko, Christopher P., Iaea, David B., Budhathoki-Uprety, Januka, Pipalia, Nina +6 more·2017·ACS Nano

Published version of a preprint

Abstract

Lipid accumulation within the lumen of endolysosomal vesicles is observed in various pathologies including atherosclerosis, liver disease, neurological disorders, lysosomal storage disorders, and cancer. Current methods cannot measure lipid flux specifically within the lysosomal lumen of live cells. We developed an optical reporter, composed of a photoluminescent carbon nanotube of a single chirality, that responds to lipid accumulation via modulation of the nanotube’s optical band gap. The engineered nanomaterial, composed of short, single-stranded DNA and a single nanotube chirality, localizes exclusively to the lumen of endolysosomal organelles without adversely affecting cell viability or proliferation or organelle morphology, integrity, or function. The emission wavelength of the reporter can be spatially resolved from within the endolysosomal lumen to generate quantitative maps of lipid content in live cells. Endolysosomal lipid accumulation in cell lines, an example of drug-induced phospholipidosis, was observed for multiple drugs in macrophages, and measurements of patient-derived Niemann–Pick type C fibroblasts identified lipid accumulation and phenotypic reversal of this lysosomal storage disease. Single-cell measurements using the reporter discerned subcellular differences in equilibrium lipid content, illuminating significant intracellular heterogeneity among endolysosomal organelles of differentiating bone-marrow-derived monocytes. Single-cell kinetics of lipoprotein-derived cholesterol accumulation within macrophages revealed rates that differed among cells by an order of magnitude. This carbon nanotube optical reporter of endolysosomal lipid content in live cells confers additional capabilities for drug development processes and the investigation of lipid-linked diseases.

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Authors
Jena, P. V., Roxbury, D., Galassi, T. V., Akkari, L., Horoszko, C. P., Iaea, D. B., Budhathoki-Uprety, J., Pipalia, N., Haka, A. S., Harvey, J. D., Mittal, J., Maxfield, F. R., Joyce, J. A., & Heller, D. A.
Affiliations
  • Memorial Sloan Kettering Cancer Center (US)
  • University of Rhode Island (US)
  • Weill Cornell Medicine (US)
  • Lehigh University (US)
Corresponding author
Heller, Daniel A.
Venue
ACS Nano
Published
2017-09-12
Volume
11
Issue
11
Pages
10689-10703
ISSN
  • 1936-0851 (ISSN-L)
  • 1936-086X
OpenAlex
W2952318715
Cited by
125
References
67
Citations by year
2026: 11 · 2025: 18 · 2024: 20 · 2023: 15 · 2022: 13 · 2021: 15 · 2020: 9 · 2019: 13 · 2018: 10 · 2017: 1
FWCI
3.81
Type
journal article
Language
en
Open access
Locations
  • ACS Nano (publishedVersion, other-oa)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Journal of Media Literacy Education (submittedVersion, cc-by)
  • IRIS (submittedVersion)
  • OSTI OAI (U.S. Department of Energy Office of Scientific and Technical Information) (submittedVersion)
  • SERVAL (Université de Lausanne) (submittedVersion)
Funders
  • American Cancer Society (NA)
  • National Heart, Lung, and Blood Institute (R01 HL093324)
  • National Cancer Institute (P30 CA008748, R01 CA148967, R01 CA181355)
  • National Institute of General Medical Sciences (P20 GM103430)
  • National Institute of Diabetes and Digestive and Kidney Diseases (F31 DK104631)
  • National Institute of Child Health and Human Development (DP2 HD075698)
  • American Brain Tumor Association (NA)
  • Ara Parseghian Medical Research Foundation (NA)
  • Commonwealth Foundation (NA)
  • Basic Energy Sciences (DE SC0013979)
  • Honorable Tina Brozman Foundation (NA)
  • Memorial Sloan-Kettering Cancer Center (NA)
  • Rhode Island Foundation (20164347)
  • Alan and Sandra Gerry Metastasis Research Initiative (NA)
  • Anna Fuller Fund (NA)
  • Expect Miracles Foundation (NA)
  • Experimental Therapeutics Centre, Agency of Science, Technology and Research (NA)
  • Louis V. Gerstner Jr. Young Investigator's Fund (NA)
Topics
  • Physical Sciences › Materials Science › Materials Chemistry › Luminescence and Fluorescent Materials
  • Physical Sciences › Engineering › Biomedical Engineering › Nanoplatforms for cancer theranostics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Calcium signaling and nucleotide metabolism
Keywords
carbon nanotubes, lipid accumulation, lysosomal storage disease, Niemann-Pick disease type C, phospholipidosis, macrophages, single-cell heterogeneity, cholesterol accumulation, lipoproteins, live-cell imaging, nanotube chirality
MeSH terms
DNA, Single-Stranded, Humans, Lipids, Luminescent Measurements, Lysosomes, Macrophages, Monocytes, Endosomes, Transport Vesicles, Nanotubes, Carbon, Atherosclerosis, Niemann-Pick Disease, Type C, Optics and Photonics, Single-Cell Analysis

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