SERS sensor based on carboxymethyl cellulose-silver hydrogel for dynamic detection of hydrogen sulfide in the inflammatory microenvironment

Accurate detection of hydrogen sulfide (H₂S) in live cells is critical for understanding its role in disease but is challenged by poor biocompatibility, signal instability, and background interference. Here, we developed a novel surface-enhanced Raman scattering (SERS) hydrogel platform based on carboxymethyl cellulose‑silver nanoparticles embedded in agarose (CMC-Ag NPs-AG). This platform is prepared via simple physical crosslinking, enabling uniform Ag NP dispersion and stable encapsulation.The hydrogel shows excellent swelling capacity, antibacterial activity (>99 % inhibition), and high biocompatibility (>98 % cell viability). Leveraging the specific formation of Ag₂S upon H₂S exposure, the platform enables ultrasensitive and selective detection. It exhibits a wide linear range (0.15–600 μM), a low detection limit of 0.15 μM, and excellent reproducibility (RSD = 1.10 %). It also demonstrates strong anti-interference performance against structurally similar sulfur-containing molecules.Furthermore, this platform was successfully applied to monitor endogenous H₂S in A549 cancer cells under varying culture conditions. The results confirm its potential for real-time, in situ detection of gaseous signaling molecules in complex biological environments. This work offers a robust and biocompatible SERS strategy for H₂S analysis and provides new insights into tumor metabolism and disease diagnosis.