Nitric Oxide(NO)is a significant gaseous signalling molecule in various pathological and physiological pathways,whereas many of its functions are still ambiguous in part because of the shortage of powerful detection approaches.Surface-enhanced Raman scattering(SERS)has distinct analysis advantages over other methods,such as fluorescence,colorimetry,and gas chromatography,in terms of its resistance to photobleaching and phototoxicity,high selectivity and sensitivity,and nondestructive detection.Herein,we present a type of reaction-based surface-enhanced Raman scattering(SERS)nanoprobes,o-phenylenediamine-modified gold nanoparticles(AuNPs/OPD),to detect the level of the endogenous NO in living cells.The detection is achieved through the SERS variation of AuNPs/OPD caused by the reaction between NO and OPD on the surface of AuNPs.The proposed SERS nanoprobes have a good stability and a rapid response to NO within 30 s.Moreover,as a result of the reaction specificity coupled with SERS fingerprinting,AuNPs/OPD nanoprobes demonstrate high selectivity towards NO over other biologically relevant species with a sensitivity at 10-7 M level.Thereby,this SERS strategy can be used for monitoring NO that is endogenously produced in living macrophages,indicating immense potential in studying NO-involved pathophysiological processes in biological systems.