In lysosomes, organelles involved in cellular trash removal, excessive lipid buildup is linked to multiple diseases, such as atherosclerosis. But detecting such accumulation, which would be advantageous for diagnosis, is difficult. Now, researchers led by Daniel A. Heller of Memorial Sloan Kettering Cancer Center and Weill Cornell Medicine have developed a nanotube assembly that senses this type of lipid accumulation in rodents (Sci. Transl. Med. 2018, DOI: 10.1126/scitranslmed.aar2680).
The nanosensor consists of one particular type of single-walled carbon nanotube noncovalently linked to DNA. After injection, the nanosensor travels to the liver, where it enters lysosomes in a specific type of cell in the liver. There, binding to lipids shifts the nanotube’s fluorescence to shorter wavelengths. The measurement “can be noninvasively detected through living tissues,” Heller says.
Heller and coworkers used the nanosensor to detect lipid accumulation in mice engineered to mimic Niemann-Pick disease, atherosclerosis, and nonalcoholic fatty liver disease (NAFLD), all of which are associated with abnormal lipid storage. The sensor picked up persistent lipid elevation in the white blood cell lysosomes of NAFLD mice fed a high-fat and high-sugar diet, even when the mice returned to a normal diet. This finding suggests prolonged effects of an unhealthful diet on the liver that is probably applicable to humans as well, Heller says.
“Such a sensor could help us find new drugs for these diseases and maybe even allow noninvasive diagnosis,” Heller adds.
CORRECTION: This story was updated on October 9, 2018, to correct the description of the nanosensor and its mechanism. The nanotubes are noncovalently linked to DNA, not covalently linked. And the sensor enters lysosomes not in a white blood cell, but a specific kind of immune cell in the liver.