Bimodal application of fluorescently labeled polymeric micelles for detection and infection-responsive therapy of Salmonella infection in a murine model

Non-typhoidal Salmonella (NTS) infection remains a significant global health concern, responsible for widespread gastroenteritis characterized by diarrhea, fever, and abdominal cramps, as well as life-threatening invasive disease in vulnerable populations. Several challenges, including reduced specificity and systemic side effects, such as disruption of the gut microbiota, limit the effectiveness of existing diagnostic and therapeutic approaches. Here, we report a multifunctional “theranostic” modality based on H 2 S-responsive fluorescent polymeric micelles (PM) for H 2 S-responsive detection and treatment of NTS infections. We synthesized a poly(ester-amide)-based amphiphilic polymer featuring H 2 S-cleavable linkers, which encapsulates ciprofloxacin (CIP) as a model antibiotic. The resulting CIP-loaded micelles (CIP@PM) are designed to respond selectively to endogenous H 2 S, a distinctive metabolic signature of NTS. To evaluate H 2 S-responsive drug release, our in vitro experiments demonstrate a fluorescence turn-on response that enables the selective detection of Salmonella -rich environments, followed by the effective killing of Salmonella by CIP released from swollen and destabilized PM. Using an in vivo murine infection model (with Salmonella Typhimurium), we further show that intragastric administration of CIP@PM significantly reduces bacterial burden in the gut and visceral organs, thereby improving overall survival. Further, we showed that, compared to free CIP, treatment with CIP@PM exhibited a modest increase in the relative abundance of beneficial gut microbiota with well-preserved intestinal tissue integrity. Together, these findings highlight the potential of H 2 S-responsive drug-loaded PM as an infection-responsive theranostic platform that combines pathogen-triggered drug release with reduced perturbation of the gut microbial ecosystem.