期刊
SCIENCE TRANSLATIONAL MEDICINE
卷 10, 期 461, 页码 -出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/scitranslmed.aar2680
关键词
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资金
- NIH New Innovator Award [DP2-HD075698]
- Cancer Center Support Grant [P30 CA008748]
- NSF CAREER Award [1752506]
- Ara Parseghian Medical Research Fund through the Michael, Marcia and Christa Parseghian Endowment for Excellence in Niemann Pick Type C Research
- Honorable Tina Brozman Foundation for Ovarian Cancer Research
- Expect Miracles Foundation-Financial Services Against Cancer
- Anna Fuller Fund
- Louis V. Gerstner Jr. Young Investigator's Fund
- Frank A. Howard Scholars Program
- Cycle for Survival
- Alan and Sandra Gerry Metastasis Research Initiative
- Commonwealth Foundation for Cancer Research
- Experimental Therapeutics Center
- Imaging and Radiation Sciences Program
- Pershing Square Sohn Cancer Research Alliance
- Department of Radiation Oncology, Research and Development funds at Memorial Sloan Kettering Cancer Center
- Center for Molecular Imaging and Nanotechnology of Memorial Sloan Kettering Cancer
- U.S. Department of Energy (DOE) Office of Science, Basic Energy Sciences (BES), and Division of Material Sciences and Engineering [DE-SC0013979]
- National Science Foundation (NSF) [TG-MCB-120014]
- Office of Science of the U.S. Department of Energy [DE-AC02-05CH11231]
- American Cancer Society Roaring Fork Valley Postdoctoral Fellowship [PF-13-388801-TBG]
- NIH National Cancer Institute T-32 fellowship [2T32CA062948-21]
- Frank Lappin Horsfall Jr. Fellowship
- [NIHNS081981]
- NATIONAL CANCER INSTITUTE [P30CA008748, T32CA062948] Funding Source: NIH RePORTER
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R01HL067773] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [K08DK101754] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [R01NS081985] Funding Source: NIH RePORTER
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.
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