Nanoconjugates of Ag/Au/Carbon Nanotube for Alkyne-Meditated Ratiometric SERS Imaging of Hypoxia in Hepatic Ischemia

Abstract

We report a ratiometric surface-enhanced Raman scattering (SERS) nanoprobe for imaging hypoxic living cells or tissues, using azo-alkynes assembled on a single-walled carbon nanotube (SWCNT) surface-functionalized with Ag/Au alloy nanoparticles (SWCNT/Ag/AuNPs). Under a hypoxic condition, azobenzene derivatives preassembled on the surface of the nanostructures are reduced stepwise by various reductases and eventually removed from the surface of the SWCNT/Ag/AuNPs, resulting in the loss of characteristic alkyne Raman bands at 2207 cm–1. Using 2D-band of SWCNTs at 2578 cm–1 as the internal standard, we are able to determine the hypoxia level based on the ratio of two peak intensities (I 2578/I 2207) as demonstrated by the successful detection in different cell lines and rat liver tissue samples derived from hepatic ischemia surgery. By combining the outstanding anti-interference property of alkynes as SERS reporters and the distinct Raman responses of alkynes and SWCNTs in complex systems, this novel ratiometric SERS strategy holds promise in becoming a very useful tool for in vitro and in vivo monitoring of hypoxia in research and clinical settings.

A decade of alkyne-tag Raman imaging (ATRI): applications in biological systems

“…126 Changes in the SERS enhancement of alkynes have also been used to monitor the cellular environment. [127][128][129] Currently we are working to develop a strategy of structural-change-based ratiometric ATRI to detect reactive biological molecules. One of the recent developments is photoswitchable Raman probes containing alkyne as reporter moiety.…”

Flexible Surface‐Enhanced Raman Scattering Substrates: A Review on Constructions, Applications, and Challenges

“…Integrating the merits of large surface area, rough surfaces, sharp corners of 2D AuNPLs, and the unique characteristics above mentioned of CNTs, the fabricated flexible SERS substrate exhibits excellent performance. Besides, AuNPs, [ 82 ] Ag/Au alloy nanoparticles, [ 83 ] and Au@Ag core/shell nanoparticles [ 84 ] have also been used as plasmonic particles to couple with CNTs. The above well‐designed SERS substrates always show excellent flexibility and sensitivity.…”

Nanoparticle‐Based Activatable Probes for Bioimaging

“…[ 86 ] Similarly, azobenzene, another well‐established hypoxia sensitive motif previously used as an imaging probe, has been incorporated in a ratiometric surface‐enhanced Raman scattering nanoprobe for imaging hypoxic living cells or tissues. [ 87 ] The azoalkynes, which have alkyne Raman bands at 2207 cm −1 , were assembled on a single‐walled carbon nanotube (SWCNT) surface‐functionalized with Ag/Au alloy nanoparticles for the first time. In the hypoxia tumor microenvironment, azoalkynes would be reduced and removed from the surface.…”

“…Thus, the hypoxia level can be determined by the ratio of two peak intensities ( I 2578 / I 2207 ). [ 87 ]…”

“…Thus, the hypoxia level can be determined by the ratio of two peak intensities (I 2578 /I 2207 ). [87] Li et al developed NIR-excited nanosensors, in which the donor and acceptor pairs within a biological metal-organic framework matrix is precisely controlled to enable upconversion fluorescence resonance energy transfer (FRET). It is suggested for detecting the O 2 concentration inside tumors with reduced signal disturbance and health detriment.…”