Nanoreporter Identifies Lysosomal Storage Disease Lipid Accumulation Intracranially

Abstract

Dysregulated lipid metabolism contributes to neurodegenerative pathologies and neurological decline in lysosomal storage disorders as well as more common neurodegenerative diseases. Niemann−Pick type A (NPA) is a fatal neurodegenerative lysosomal storage disease characterized by abnormal sphingomyelin accumulation in the endolysosomal lumen. The ability to monitor abnormalities in lipid homeostasis intracranially could improve basic investigations and the development of effective treatment strategies. We investigated the carbon nanotube-based detection of intracranial lipid content. We found that the near-infrared emission of a carbon nanotube-based lipid sensor responds to lipid accumulation in neuronal and in vivo models of NPA. The nanosensor detected lipid accumulation intracranially in an acid sphingomyelinase knockout mouse via noninvasive near-infrared spectroscopy. This work indicates a tool to improve drug development processes in NPA, other lysosomal storage diseases, and neurodegenerative diseases.

Identification of early-stage liver fibrosis by modifications in the interstitial space diffusive microenvironment using fluorescent single-walled carbon nanotubes

“…Their high brightness and spectacular photostability further allowed single particles detection beyond 50μm deep into tissue slices 3 . In addition, the versality of chiral structures provides several choices of excitation and emission schemes that can be tuned to the tissue's optical properties 4 , while the possibility to modulate their fluorescence properties by molecular interactions has also allowed detecting the presence of analytes 5 which can be markers for functional events or diseased states [6][7][8] .…”

“…Their high brightness and spectacular photostability further allowed single particles detection beyond 50μm deep into tissue slices 3 . In addition, the versality of chiral structures provides several choices of excitation and emission schemes that can be tuned to the tissue's optical properties 4 , while the possibility to modulate their fluorescence properties by molecular interactions has also allowed detecting the presence of analytes 5 which can be markers for functional events or diseased states [6][7][8] In this work, we rely on an additional potentiality of SWCNTs formerly demonstrated in brain tissue 3,9,10 , namely, their ability to be detected at the single particle level while they move in the interstitial spaces of live tissue, and thus to access local diffusional environments. This is due to the combination of a nanometric cross-section, which lets the nanotube explore much of the interstitial space without getting stuck, and a micrometric length, which slows down their motion to make fluorescence tracking possible.…”

Identification of Early Stage Liver Fibrosis by Modifications in the Interstitial Space Diffusive Microenvironment Using Fluorescent Single-Walled Carbon Nanotubes

“…In addition, the versatility of chiral structures provides several choices of excitation and emission schemes that can be optimized given the tissue’s optical properties . Finally, the possibility to modulate their fluorescence properties by molecular interactions allows the detection of analytes, which can be markers for functional events or diseased states. − …”

Monitoring Enzyme Activity Using Near-Infrared Fluorescent Single-Walled Carbon Nanotubes

“… 28 , 38 − 46 These include the high surface area and the ease of surface functionalization with molecules of choice that facilitate interaction with a large number of analytes, enabling high-throughput readouts. 47 − 56 Moreover, SWCNTs exhibit remarkable photo and chemical stability, rendering them a compelling choice as sensors for monitoring essential biomarkers, including proteins, 57 − 66 oncometabolites, 67 pathogens, 68 , 69 various small molecules, 70 − 77 hormones, 58 , 78 , 79 volatiles, 80 , 81 lipids, 44 , 82 , 83 sugars, 84 − 89 neurotransmitters, 30 , 34 , 90 − 94 microRNA, 95 , 96 metal ions, 97 lysosomal pH, 98 and enzymatic activity and inhibition. 99 − 107 …”

“…In light of these considerations, the significance of luminescent probes operating in the near-infrared (NIR) region becomes evident. These probes offer real-time and spatiotemporal information, and their utility is particularly notable because biological samples are mostly transparent in the NIR region. − In pursuit of this objective, NIR luminescent single-walled carbon nanotubes (SWCNTs) are advantageous due to their intrinsic physicochemical and optical properties. ,− These include the high surface area and the ease of surface functionalization with molecules of choice that facilitate interaction with a large number of analytes, enabling high-throughput readouts. − Moreover, SWCNTs exhibit remarkable photo and chemical stability, rendering them a compelling choice as sensors for monitoring essential biomarkers, including proteins, − oncometabolites, pathogens, , various small molecules, − hormones, ,, volatiles, , lipids, ,, sugars, − neurotransmitters, ,,− microRNA, , metal ions, lysosomal pH, and enzymatic activity and inhibition. −…”