Advances in surface-coated single-walled carbon nanotubes as near-infrared photoluminescence emitters for single-particle tracking applications in biological environments

Abstract

Single-particle tracking (SPT) represents a powerful tool for revealing the single-molecule dynamics in a number of biological processes in live cells and biological tissue. Single-walled carbon nanotubes (SWCNTs) are promising photoluminescence emitters for SPT applications in various biological environments due to their characteristic large-aspect-ratio structures along with their bright and stable near-infrared (NIR) photoluminescence, which are invaluable for long-term video-rate imaging and tracking applications at the single-molecule level with high signal-to-noise ratios (SNRs). Recent advances in applying SWCNTs as NIR photoluminescence emitters have highlighted the understanding of brain tissue organization at the nanometer scale. In the first section, this review article summarizes the latest advances in different surface coatings commonly used for encapsulating SWCNT surfaces via molecular self-assembly in order to obtain surface-coated nanotubes with low cytotoxicity and minimal nonspecific interactions with live cells while maintaining their emission of bright photoluminescence to enable long-term photoluminescent imaging and tracking at the single-nanotube level in biological environments. The second section offers a comparison of different excitation strategies of (6,5) SWCNTs to determine the best excitation wavelength for efficient video-rate imaging and tracking of individual nanotubes in live brain tissue for up to tens of minutes without inducing unacceptable phototoxicity or temperature increases. Finally, this review showcases that, by utilizing the photoluminescence tracking of single nanotubes combined with super-resolution single-molecule localization microscopy technologies, it is practical to elucidate the ultrafine nanometer-scale organization of the brain extracellular space (ECS) and probe the local rheological properties of young rat brain with a subdiffraction optical resolution down to 50 nm at a subwavelength accuracy of ~40 nm. The findings primarily indicate the great diversity of the brain ECS and the inhomogeneous properties of the local viscosity in live brain tissue. Overall, because of their advantages of low cytotoxicity, bright photoluminescence, high SNRs (~25), and deep tissue penetration (~100 μm) for long-term video-rate imaging and tracking at the single-nanotube level under 845 nm excitation (K-momentum exciton–phonon sideband, KSB), phospholipid-polyethylene glycol-coated SWCNTs hold great potential as NIR photoluminescence emitters for single-particle tracking in biological environments, as exemplified here in live brain tissue, and may find extended applications in elucidating the fundamental roles of the brain ECS in various biological processes, such as sleep, memory, aging, brain tumor progression, and neurodegenerative disease development.