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Title: An optical nanoreporter of endolysosomal lipid accumulation reveals enduring effects of diet on hepatic macrophages in vivo

Abstract

The abnormal accumulation of lipids within the endolysosomal lumen occurs in many conditions, including lysosomal storage disorders, atherosclerosis, nonalcoholic fatty liver disease (NAFLD), and drug-induced phospholipidosis. Current methods cannot monitor endolysosomal lipid content in vivo, hindering preclinical drug development and research into the mechanisms linking endolysosomal lipid accumulation to disease progression. We developed a single-walled carbon nanotube–based optical reporter that noninvasively measures endolysosomal lipid accumulation via bandgap modulation of its intrinsic near-infrared emission. The reporter detected lipid accumulation in Niemann-Pick disease, atherosclerosis, and NAFLD models in vivo. By applying the reporter to the study of NAFLD, we found that elevated lipid quantities in hepatic macrophages caused by a high-fat diet persist long after reverting to a normal diet. The reporter dynamically monitored endolysosomal lipid accumulation in vivo over time scales ranging from minutes to weeks, indicating its potential to accelerate preclinical research and drug development processes.

Authors:
ORCiD logo [1]; ORCiD logo [2];  [2]; ORCiD logo [3];  [4]; ORCiD logo [5];  [5]; ORCiD logo [5];  [5];  [4];  [2];  [6];  [7];  [3];  [5]; ORCiD logo [1]
  1. Memorial Sloan Kettering Cancer Center, New York, NY (United States); Weill Cornell Medicine, New York, NY (United States)
  2. Memorial Sloan Kettering Cancer Center, New York, NY (United States)
  3. National Inst. of Standards and Technology (NIST), Gaithersburg, MD (United States)
  4. Washington Univ., St. Louis, MO (United States). School of Medicine
  5. Weill Cornell Medicine, New York, NY (United States)
  6. Univ. of Rhode Island, Narragansett, RI (United States)
  7. Lehigh Univ., Bethlehem, PA (United States)
Publication Date:
Research Org.:
Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States). National Energy Research Scientific Computing Center (NERSC); Univ. of California, Oakland, CA (United States); Lehigh Univ., Bethlehem, PA (United States)
Sponsoring Org.:
USDOE Office of Science (SC)
OSTI Identifier:
1475480
Alternate Identifier(s):
OSTI ID: 1544006
Grant/Contract Number:  
AC02-05CH11231; SC0013979
Resource Type:
Published Article
Journal Name:
Science Translational Medicine
Additional Journal Information:
Journal Volume: 10; Journal Issue: 461; Journal ID: ISSN 1946-6234
Publisher:
AAAS
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; Cell Biology; Research & Experimental Medicine

Citation Formats

Galassi, Thomas V., Jena, Prakrit V., Shah, Janki, Ao, Geyou, Molitor, Elizabeth, Bram, Yaron, Frankel, Angela, Park, Jiwoon, Jessurun, Jose, Ory, Daniel S., Haimovitz-Friedman, Adriana, Roxbury, Daniel, Mittal, Jeetain, Zheng, Ming, Schwartz, Robert E., and Heller, Daniel A. An optical nanoreporter of endolysosomal lipid accumulation reveals enduring effects of diet on hepatic macrophages in vivo. United States: N. p., 2018. Web. doi:10.1126/scitranslmed.aar2680.
Galassi, Thomas V., Jena, Prakrit V., Shah, Janki, Ao, Geyou, Molitor, Elizabeth, Bram, Yaron, Frankel, Angela, Park, Jiwoon, Jessurun, Jose, Ory, Daniel S., Haimovitz-Friedman, Adriana, Roxbury, Daniel, Mittal, Jeetain, Zheng, Ming, Schwartz, Robert E., & Heller, Daniel A. An optical nanoreporter of endolysosomal lipid accumulation reveals enduring effects of diet on hepatic macrophages in vivo. United States. doi:10.1126/scitranslmed.aar2680.
Galassi, Thomas V., Jena, Prakrit V., Shah, Janki, Ao, Geyou, Molitor, Elizabeth, Bram, Yaron, Frankel, Angela, Park, Jiwoon, Jessurun, Jose, Ory, Daniel S., Haimovitz-Friedman, Adriana, Roxbury, Daniel, Mittal, Jeetain, Zheng, Ming, Schwartz, Robert E., and Heller, Daniel A. Wed . "An optical nanoreporter of endolysosomal lipid accumulation reveals enduring effects of diet on hepatic macrophages in vivo". United States. doi:10.1126/scitranslmed.aar2680.
@article{osti_1475480,
title = {An optical nanoreporter of endolysosomal lipid accumulation reveals enduring effects of diet on hepatic macrophages in vivo},
author = {Galassi, Thomas V. and Jena, Prakrit V. and Shah, Janki and Ao, Geyou and Molitor, Elizabeth and Bram, Yaron and Frankel, Angela and Park, Jiwoon and Jessurun, Jose and Ory, Daniel S. and Haimovitz-Friedman, Adriana and Roxbury, Daniel and Mittal, Jeetain and Zheng, Ming and Schwartz, Robert E. and Heller, Daniel A.},
abstractNote = {The abnormal accumulation of lipids within the endolysosomal lumen occurs in many conditions, including lysosomal storage disorders, atherosclerosis, nonalcoholic fatty liver disease (NAFLD), and drug-induced phospholipidosis. Current methods cannot monitor endolysosomal lipid content in vivo, hindering preclinical drug development and research into the mechanisms linking endolysosomal lipid accumulation to disease progression. We developed a single-walled carbon nanotube–based optical reporter that noninvasively measures endolysosomal lipid accumulation via bandgap modulation of its intrinsic near-infrared emission. The reporter detected lipid accumulation in Niemann-Pick disease, atherosclerosis, and NAFLD models in vivo. By applying the reporter to the study of NAFLD, we found that elevated lipid quantities in hepatic macrophages caused by a high-fat diet persist long after reverting to a normal diet. The reporter dynamically monitored endolysosomal lipid accumulation in vivo over time scales ranging from minutes to weeks, indicating its potential to accelerate preclinical research and drug development processes.},
doi = {10.1126/scitranslmed.aar2680},
journal = {Science Translational Medicine},
number = 461,
volume = 10,
place = {United States},
year = {2018},
month = {10}
}

Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record
DOI: 10.1126/scitranslmed.aar2680

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Cited by: 4 works
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