Cell membrane-targeted surface enhanced Raman scattering nanoprobes for the monitoring of hydrogen sulfide secreted from living cells.

Hydrogen sulfide (H ₂ S), an important gas signal molecule, participates in intercellular signal transmission and plays a considerable role in physiology and pathology. However, in-situ monitoring of H ₂ S level during the processes of material transport between cells remains considerably challenging. Herein, a cell membrane-targeted surface-enhanced Raman scattering (SERS) nanoprobe was designed to quantitatively detect H ₂ S secreted from living cells. The nanoprobes were fabricated by assembling cholesterol-functionalized DNA strands and dithiobis(phenylazide) (DTBPA) molecules on core-shell gold nanostars embedded with 4-mercaptoacetonitrile (4-MBN) (AuNPs@4-MBN@Au). Thus, three functions including cell-membrane targeted via cholesterol, internal standard calibration, and responsiveness to H ₂ S through reduction of azide group in DTBPA molecules were integrated into the nanoprobes. In addition, the nanoprobes can quickly respond to H ₂ S within 90 s and sensitively, selectively, and reliably detect H ₂ S with a limit of detection as low as 37 nM due to internal standard-assisted calibration and reaction specificity. Moreover, the nanoprobes can effectively target on cell membrane and realize SERS visualization of dynamic H ₂ S released from HeLa cells. By employing the proposed approach, an intriguing phenomenon was observed: the other two major endogenous gas transmitters, carbon monoxide (CO) and nitric oxide (NO), exhibited opposite effect on H ₂ S production in living cells stimulated by related gas release molecules. In particular, the introduction of CO inhibited the generation of H ₂ S in HeLa cells, while NO promoted its output. Thus, the nanoprobes can provide a robust method for investigating H ₂ S-related extracellular metabolism and intercellular signaling transmission.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier B.V. All rights reserved.)