On-demand H₂S delivery from NIR-activated dithiocarbamate-functionalized AuAg microdroplets for cellular anti-inflammation.

The development of microscale biocompatible systems for precise regulation of biological processes presents considerable challenges, particularly in achieving spatiotemporal control over gaseous signaling molecules. In this work, we engineered coacervate microspheres through a self-assembly approach to co-encapsulate a hydrogen sulfide (H₂S) donor, histidine dithiocarbamate (His-DTC), together with near-infrared (NIR)-responsive gold-silver alloy nanoparticles (Au@Au/Ag NPs). These microspheres, with an average diameter of 13.6 ± 3.5 μm, exhibited strong photothermal conversion under 780 nm NIR irradiation, triggering the thermal decomposition of His-DTC and enabling controlled H₂S release. The optimized coacervate microdroplets enabled efficient, NIR-triggered release of physiologically significant amounts of H₂S, as quantified by fluorescence spectroscopy. In co-culture experiments with CEM cells, this release effectively elevated intracellular H₂S levels and activated the NRF2-HO-1-NQO1 pathway to exert potent anti-inflammatory effects. This remote-controlled and on-demand platform provides a novel strategy for the intelligent modulation of H₂S, offering broad potential for studying gasotransmitter-mediated cellular responses.