Safeguarding the Photoluminescence of Silver Sulfide Nanocrystals in Biological Environments via Silica Shielding

ABSTRACT Near‐infrared (NIR)‐emitting Ag 2 S nanocrystals (NCs) are promising contrast agents in nanomedicine, thanks to extensive efforts to improve their photochemical stability, biocompatibility, and brightness by tuning their size, composition, surface chemistry, and core/shell architecture. However, when dispersed in biological media, these NCs undergo non‐specific interactions with surrounding species, including biomolecules. Such interactions may compromise their colloidal and physicochemical stability, alter their photoluminescence properties, and impair both in vitro and in vivo imaging and sensing performance. Here, we show that incorporating NIR‐emitting Ag 2 S‐based NCs into colloidal dendritic silica effectively minimizes environmental interference in complex biological media, including blood plasma and whole blood. Steady‐state and time‐resolved photoluminescence measurements reveal that both emission intensity and lifetime are substantially better preserved following incorporation into silica colloids. This preservation has a dual benefit: maintaining photoluminescence intensity enables precise NIR imaging, while retention of spectral and temporal responses preserves the NCs’ thermal sensing capability. Proof‐of‐concept experiments in tissue phantoms and small‐animal models confirm these findings. The approach supports reliable optical readouts under biologically relevant conditions without modifying the NC composition. Overall, incorporation into dendritic silica colloids offers a viable strategy for protecting luminescent nanoparticles from biological interference and retaining their optical properties for biomedical imaging and sensing applications.