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

Nano Lett. 2024 May 8;24(18):5603-5609. doi: 10.1021/acs.nanolett.4c00955. Epub 2024 Apr 26.

Abstract

During liver fibrosis, recurrent hepatic injuries lead to the accumulation of collagen and other extracellular matrix components in the interstitial space, ultimately disrupting liver functions. Early stages of liver fibrosis may be reversible, but opportunities for diagnosis at these stages are currently limited. Here, we show that the alterations of the interstitial space associated with fibrosis can be probed by tracking individual fluorescent single-walled carbon nanotubes (SWCNTs) diffusing in that space. In a mouse model of early liver fibrosis, we find that nanotubes generally explore elongated areas, whose lengths decrease as the disease progresses, even in regions where histopathological examination does not reveal fibrosis yet. Furthermore, this decrease in nanotube mobility is a purely geometrical effect as the instantaneous nanotube diffusivity stays unmodified. This work establishes the promise of SWCNTs both for diagnosing liver fibrosis at an early stage and for more in-depth studies of the biophysical effects of the disease.

Keywords: carbon nanotube fluorescence; diffusion; interstitial space; liver fibrosis; single-particle tracking; tissue nanostructure.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Diffusion
  • Disease Models, Animal
  • Extracellular Matrix / metabolism
  • Fluorescent Dyes / chemistry
  • Liver / pathology
  • Liver Cirrhosis* / pathology
  • Mice
  • Nanotubes, Carbon* / chemistry

Substances

  • Nanotubes, Carbon
  • Fluorescent Dyes