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

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.

doi:10.1126/scitranslmed.aar2680

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

Journal Article · 02 October 2018 · Science Translational Medicine

DOI: https://doi.org/10.1126/scitranslmed.aar2680 · OSTI ID:1475480

;

; Shah, Janki;

; Molitor, Elizabeth;

; Frankel, Angela;

; Jessurun, Jose; Ory, Daniel S.; Haimovitz-Friedman, Adriana; Roxbury, Daniel; Mittal, Jeetain; Zheng, Ming; Schwartz, Robert E.;

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.

View Journal Article

Cite

Export

Save

Research Organization:: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States). National Energy Research Scientific Computing Center (NERSC); Lehigh Univ., Bethlehem, PA (United States); Univ. of California, Oakland, CA (United States)

Sponsoring Organization:: USDOE; USDOE Office of Science (SC)

Grant/Contract Number:: AC02-05CH11231; SC0013979

OSTI ID:: 1475480

Journal Information:: Science Translational Medicine, Journal Name: Science Translational Medicine Journal Issue: 461 Vol. 10; ISSN 1946-6234

Publisher:: American Association for the Advancement of Science (AAAS)Copyright Statement

Country of Publication:: United States

Language:: English

References (55)

Preparation and Separation of DNA-Wrapped Carbon Nanotubes: DNA-Wrapped Carbon Nanotubes Ao, Geyou; Zheng, Ming Current Protocols in Chemical Biology, Vol. 7, Issue 1 https://doi.org/10.1002/9780470559277.ch140099	journal	March 2015
Intracoronary Near-Infrared Spectroscopy (NIRS) Imaging for Detection of Lipid Content of Coronary Plaques: Current Experience and Future Perspectives Jaguszewski, Milosz; Klingenberg, Roland; Landmesser, Ulf Current Cardiovascular Imaging Reports, Vol. 6, Issue 5 https://doi.org/10.1007/s12410-013-9224-2	journal	August 2013
The organ distribution and circulation time of intravenously injected colloidal carriers sterically stabilized with a blockcopolymer - poloxamine 908 Illum, Lisbeth; Davis, S. S.; Müller, R. H. Life Sciences, Vol. 40, Issue 4 https://doi.org/10.1016/0024-3205(87)90138-X	journal	January 1987
VMD: Visual molecular dynamics Humphrey, William; Dalke, Andrew; Schulten, Klaus Journal of Molecular Graphics, Vol. 14, Issue 1 https://doi.org/10.1016/0263-7855(96)00018-5	journal	February 1996
Replica-exchange molecular dynamics method for protein folding Sugita, Yuji; Okamoto, Yuko Chemical Physics Letters, Vol. 314, Issue 1-2 https://doi.org/10.1016/S0009-2614(99)01123-9	journal	November 1999
Pathology of Visceral Organs and Bone Marrow in an Acid Sphingomyelinase Deficient Knock-Out Mouse Line, Mimicking Human Niemann-Pick Disease Type A Kuemmel, T. A.; Thiele, J.; Schroeder, R. Pathology - Research and Practice, Vol. 193, Issue 10 https://doi.org/10.1016/S0344-0338(97)80025-8	journal	January 1997
The controlled intravenous delivery of drugs using PEG-coated sterically stabilized nanospheres Gref, R.; Domb, A.; Quellec, P. Advanced Drug Delivery Reviews, Vol. 64 https://doi.org/10.1016/j.addr.2012.09.008	journal	December 2012
Opsonization, biodistribution, and pharmacokinetics of polymeric nanoparticles Owensiii, D.; Peppas, N. International Journal of Pharmaceutics, Vol. 307, Issue 1 https://doi.org/10.1016/j.ijpharm.2005.10.010	journal	January 2006
A diet-induced animal model of non-alcoholic fatty liver disease and hepatocellular cancer Asgharpour, Amon; Cazanave, Sophie C.; Pacana, Tommy Journal of Hepatology, Vol. 65, Issue 3 https://doi.org/10.1016/j.jhep.2016.05.005	journal	September 2016
Cholesterol metabolism and the pathogenesis of non-alcoholic steatohepatitis Musso, Giovanni; Gambino, Roberto; Cassader, Maurizio Progress in Lipid Research, Vol. 52, Issue 1 https://doi.org/10.1016/j.plipres.2012.11.002	journal	January 2013
Biomarkers to monitor drug-induced phospholipidosis Baronas, E.; Lee, J.; Alden, C. Toxicology and Applied Pharmacology, Vol. 218, Issue 1 https://doi.org/10.1016/j.taap.2006.10.015	journal	January 2007
Di-22:6-bis(monoacylglycerol)phosphate: A clinical biomarker of drug-induced phospholipidosis for drug development and safety assessment Liu, Nanjun; Tengstrand, Elizabeth A.; Chourb, Lisa Toxicology and Applied Pharmacology, Vol. 279, Issue 3 https://doi.org/10.1016/j.taap.2014.06.014	journal	September 2014
Emerging Technologies and their Applications in Lipid Compartment Measurement Heymsfield, Steven B.; Hu, Houchun Harry; Shen, Wei Trends in Endocrinology & Metabolism, Vol. 26, Issue 12 https://doi.org/10.1016/j.tem.2015.10.003	journal	December 2015
Evaluation and validation of multiple cell lines and primary mouse macrophages to predict phospholipidosis potential LeCureux, Lloyd; Cheng, Charles S.; Herbst, John Toxicology in Vitro, Vol. 25, Issue 8 https://doi.org/10.1016/j.tiv.2011.06.017	journal	December 2011
A Carbon Nanotube Optical Sensor Reports Nuclear Entry via a Noncanonical Pathway Budhathoki-Uprety, Januka; Langenbacher, Rachel E.; Jena, Prakrit V. ACS Nano, Vol. 11, Issue 4 https://doi.org/10.1021/acsnano.7b00176	journal	April 2017
A Carbon Nanotube Optical Reporter Maps Endolysosomal Lipid Flux Jena, Prakrit V.; Roxbury, Daniel; Galassi, Thomas V. ACS Nano, Vol. 11, Issue 11 https://doi.org/10.1021/acsnano.7b04743	journal	September 2017
Sequence-Specific Self-Stitching Motif of Short Single-Stranded DNA on a Single-Walled Carbon Nanotube Roxbury, Daniel; Jagota, Anand; Mittal, Jeetain Journal of the American Chemical Society, Vol. 133, Issue 34 https://doi.org/10.1021/ja204413v	journal	August 2011
DNA-Controlled Partition of Carbon Nanotubes in Polymer Aqueous Two-Phase Systems Ao, Geyou; Khripin, Constantine Y.; Zheng, Ming Journal of the American Chemical Society, Vol. 136, Issue 29 https://doi.org/10.1021/ja504078b	journal	July 2014
Differentiating Left- and Right-Handed Carbon Nanotubes by DNA Ao, Geyou; Streit, Jason K.; Fagan, Jeffrey A. Journal of the American Chemical Society, Vol. 138, Issue 51 https://doi.org/10.1021/jacs.6b09135	journal	December 2016
Thiadiazole Carbamates: Potent Inhibitors of Lysosomal Acid Lipase and Potential Niemann−Pick Type C Disease Therapeutics Rosenbaum, Anton I.; Cosner, Casey C.; Mariani, Christopher J. Journal of Medicinal Chemistry, Vol. 53, Issue 14 https://doi.org/10.1021/jm100499s	journal	July 2010
Molecular-Basis of Single-Walled Carbon Nanotube Recognition by Single-Stranded DNA Roxbury, Daniel; Mittal, Jeetain; Jagota, Anand Nano Letters, Vol. 12, Issue 3 https://doi.org/10.1021/nl204182b	journal	February 2012
DNA sequence motifs for structure-specific recognition and separation of carbon nanotubes Tu, Xiaomin; Manohar, Suresh; Jagota, Anand Nature, Vol. 460, Issue 7252, p. 250-253 https://doi.org/10.1038/nature08116	journal	July 2009
Acid sphingomyelinase deficient mice: a model of types A and B Niemann–Pick disease Horinouchi, Kenichi; Erlich, Shai; Perl, Daniel P. Nature Genetics, Vol. 10, Issue 3 https://doi.org/10.1038/ng0795-288	journal	July 1995
The role of autophagy in neurodegenerative disease Nixon, Ralph A. Nature Medicine, Vol. 19, Issue 8 https://doi.org/10.1038/nm.3232	journal	August 2013
Fiji: an open-source platform for biological-image analysis Schindelin, Johannes; Arganda-Carreras, Ignacio; Frise, Erwin Nature Methods, Vol. 9, Issue 7 https://doi.org/10.1038/nmeth.2019	journal	June 2012
A pilot toxicology study of single-walled carbon nanotubes in a small sample of mice Schipper, Meike L.; Nakayama-Ratchford, Nozomi; Davis, Corrine R. Nature Nanotechnology, Vol. 3, Issue 4 https://doi.org/10.1038/nnano.2008.68	journal	March 2008
In vivo biosensing via tissue-localizable near-infrared-fluorescent single-walled carbon nanotubes Iverson, Nicole M.; Barone, Paul W.; Shandell, Mia Nature Nanotechnology, Vol. 8, Issue 11 https://doi.org/10.1038/nnano.2013.222	journal	November 2013
Single-nanotube tracking reveals the nanoscale organization of the extracellular space in the live brain Godin, Antoine G.; Varela, Juan A.; Gao, Zhenghong Nature Nanotechnology, Vol. 12, Issue 3 https://doi.org/10.1038/nnano.2016.248	journal	November 2016
Preparation of cells for assessing ultrastructural localization of nanoparticles with transmission electron microscopy Schrand, Amanda M.; Schlager, John J.; Dai, Liming Nature Protocols, Vol. 5, Issue 4 https://doi.org/10.1038/nprot.2010.2	journal	March 2010
High-yield and high-purity isolation of hepatic stellate cells from normal and fibrotic mouse livers Mederacke, Ingmar; Dapito, Dianne H.; Affò, Silvia Nature Protocols, Vol. 10, Issue 2 https://doi.org/10.1038/nprot.2015.017	journal	January 2015
The cell biology of lysosomal storage disorders Futerman, Anthony H.; van Meer, Gerrit Nature Reviews Molecular Cell Biology, Vol. 5, Issue 7 https://doi.org/10.1038/nrm1423	journal	July 2004
A carbon nanotube reporter of microRNA hybridization events in vivo Harvey, Jackson D.; Jena, Prakrit V.; Baker, Hanan A. Nature Biomedical Engineering, Vol. 1, Issue 4 https://doi.org/10.1038/s41551-017-0041	journal	March 2017
Hyperspectral Microscopy of Near-Infrared Fluorescence Enables 17-Chirality Carbon Nanotube Imaging Roxbury, Daniel; Jena, Prakrit V.; Williams, Ryan M. Scientific Reports, Vol. 5, Issue 1 https://doi.org/10.1038/srep14167	journal	September 2015
Spectral triangulation: a 3D method for locating single-walled carbon nanotubes in vivo Lin, Ching-Wei; Bachilo, Sergei M.; Vu, Michael Nanoscale, Vol. 8, Issue 19 https://doi.org/10.1039/C6NR01376G	journal	January 2016
Abnormal Lipid and Glucose Metabolism in Obesity: Implications for Nonalcoholic Fatty Liver Disease Parekh, Samir; Anania, Frank A. Gastroenterology, Vol. 132, Issue 6 https://doi.org/10.1053/j.gastro.2007.03.055	journal	May 2007
Comparison of simple potential functions for simulating liquid water Jorgensen, William L.; Chandrasekhar, Jayaraman; Madura, Jeffry D. The Journal of Chemical Physics, Vol. 79, Issue 2 https://doi.org/10.1063/1.445869	journal	July 1983
Circulation and long-term fate of functionalized, biocompatible single-walled carbon nanotubes in mice probed by Raman spectroscopy Liu, Z.; Davis, C.; Cai, W. Proceedings of the National Academy of Sciences, Vol. 105, Issue 5 https://doi.org/10.1073/pnas.0707654105	journal	January 2008
Endocytosis of beta-cyclodextrins is responsible for cholesterol reduction in Niemann-Pick type C mutant cells Rosenbaum, A. I.; Zhang, G.; Warren, J. D. Proceedings of the National Academy of Sciences, Vol. 107, Issue 12 https://doi.org/10.1073/pnas.0914309107	journal	March 2010
Letter to the Editor Berridge, Brian R.; Chatman, Linda A.; Odin, Marielle Toxicologic Pathology, Vol. 35, Issue 2 https://doi.org/10.1080/01926230701196414	journal	February 2007
Niemann-Pick type C disease: molecular mechanisms and potential therapeutic approaches: Therapeutics for NPC disease Rosenbaum, Anton I.; Maxfield, Frederick R. Journal of Neurochemistry, Vol. 116, Issue 5 https://doi.org/10.1111/j.1471-4159.2010.06976.x	journal	January 2011
Trapping of oxidized LDL in lysosomes of Kupffer cells is a trigger for hepatic inflammation Bieghs, Veerle; Walenbergh, Sofie M. A.; Hendrikx, Tim Liver International, Vol. 33, Issue 7 https://doi.org/10.1111/liv.12170	journal	April 2013
Lysosomal cholesterol accumulation: driver on the road to inflammation during atherosclerosis and non-alcoholic steatohepatitis: Lysosomal cholesterol during obesity Hendrikx, T.; Walenbergh, S. M. A.; Hofker, M. H. Obesity Reviews, Vol. 15, Issue 5 https://doi.org/10.1111/obr.12159	journal	March 2014
Noninvasive ovarian cancer biomarker detection via an optical nanosensor implant Williams, Ryan M.; Lee, Christopher; Galassi, Thomas V. Science Advances, Vol. 4, Issue 4 https://doi.org/10.1126/sciadv.aaq1090	journal	April 2018
Band Gap Fluorescence from Individual Single-Walled Carbon Nanotubes O'Connell, Michael J.; Bachilo, Sergei M.; Huffman, Chad B. Science, Vol. 297, Issue 5581, p. 593-596 https://doi.org/10.1126/science.1072631	journal	July 2002
Structure-Assigned Optical Spectra of Single-Walled Carbon Nanotubes Bachilo, S. M. Science, Vol. 298, Issue 5602 https://doi.org/10.1126/science.1078727	journal	November 2002
Biodegradable long-circulating polymeric nanospheres Gref, R.; Minamitake, Y.; Peracchia, M. Science, Vol. 263, Issue 5153 https://doi.org/10.1126/science.8128245	journal	March 1994
Severe NAFLD with hepatic necroinflammatory changes in mice fed trans fats and a high-fructose corn syrup equivalent Tetri, Laura H.; Basaranoglu, Metin; Brunt, Elizabeth M. American Journal of Physiology-Gastrointestinal and Liver Physiology, Vol. 295, Issue 5 https://doi.org/10.1152/ajpgi.90272.2008	journal	November 2008
Enzyme deficiency in cholesteryl ester storage disease Sloan, Howard R.; Fredrickson, Donald S. Journal of Clinical Investigation, Vol. 51, Issue 7 https://doi.org/10.1172/JCI106997	journal	July 1972
A Strategy for Risk Management of Drug-Induced Phospholipidosis Chatman, Linda A.; Morton, Daniel; Johnson, Theodore O. Toxicologic Pathology, Vol. 37, Issue 7 https://doi.org/10.1177/0192623309352496	journal	December 2009
Internalization of Modified Lipids by CD36 and SR-A Leads to Hepatic Inflammation and Lysosomal Cholesterol Storage in Kupffer Cells Bieghs, Veerle; Verheyen, Fons; van Gorp, Patrick J. PLoS ONE, Vol. 7, Issue 3 https://doi.org/10.1371/journal.pone.0034378	journal	March 2012
A Murine Niemann-Pick C1 I1061T Knock-In Model Recapitulates the Pathological Features of the Most Prevalent Human Disease Allele Praggastis, M.; Tortelli, B.; Zhang, J. Journal of Neuroscience, Vol. 35, Issue 21 https://doi.org/10.1523/JNEUROSCI.4173-14.2015	journal	May 2015
High Fat Diet Induced Hepatic Steatosis Establishes a Permissive Microenvironment for Colorectal Metastases and Promotes Primary Dysplasia in a Murine Model VanSaun, Michael Nathan; Lee, In Kyu; Washington, Mary Kay The American Journal of Pathology, Vol. 175, Issue 1 https://doi.org/10.2353/ajpath.2009.080703	journal	July 2009
Inhibition of acid sphingomyelinase by tricyclic antidepressants and analogons Beckmann, Nadine; Sharma, Deepa; Gulbins, Erich Frontiers in Physiology, Vol. 5 https://doi.org/10.3389/fphys.2014.00331	journal	September 2014
Assessment of Coronary Atherosclerosis using Optical Coherence Tomography Kubo, Takashi; Tanaka, Atsushi; Ino, Yasushi Journal of Atherosclerosis and Thrombosis, Vol. 21, Issue 9 https://doi.org/10.5551/jat.25452	journal	January 2014
Identification of NPC1 as the target of U18666A, an inhibitor of lysosomal cholesterol export and Ebola infection Lu, Feiran; Liang, Qiren; Abi-Mosleh, Lina eLife, Vol. 4 https://doi.org/10.7554/eLife.12177	journal	December 2015

Similar Records

Inhibition of mTOR improves the impairment of acidification in autophagic vesicles caused by hepatic steatosis

Journal Article · 2016 · Biochemical and Biophysical Research Communications · OSTI ID:22594200

Nakadera, Eisuke; Yamashina, Shunhei; Izumi, Kousuke; +7 more

GLP-1 analogue improves hepatic lipid accumulation by inducing autophagy via AMPK/mTOR pathway

Journal Article · 2016 · Biochemical and Biophysical Research Communications · OSTI ID:22598786

He, Qin; Sha, Sha; Sun, Lei; +2 more

Gene Expression and DNA Methylation Alterations in the Glycine N-Methyltransferase Gene in Diet-Induced Nonalcoholic Fatty Liver Disease-Associated Carcinogenesis

Journal Article · 2019 · Toxicological Sciences · OSTI ID:1565976

Borowa-Mazgaj, Barbara; de Conti, Aline; Tryndyak, Volodymyr; +9 more

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
Cell Biology
Research & Experimental Medicine

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

Citation Formats

References (55)

Similar Records

Related Subjects