Introduction: Niclosamide (NIC) has significant potential as a clinical therapeutic agent for Clostridioides difficile infection (CDI); however, its strong hydrophobicity hampers its oral bioavailability, and its active effects against C. difficile remain unclear.Methods: Niclosamide-loaded controlled-release hyaluronic acid-modified poly (lactic-co-glycolic acid) naosphernes (NIC@PLGA-HAs) were synthesized using an oil-in-water emulsion technique and their effects on C. difficile cell growth, spore germination, biofilm formation, and NIC interaction sites with C. difficile toxin B (TcdB) were analyzed.Results: NIC@PLGA-HAs exhibited enhanced solubility and stability, with a water contact angle on a hydrophilic surface of 65.1° and a zeta potential of 31.57 ± 2.08 mV, and pH-responsive (pH 7.4) controlled-release characteristics compared to free NIC. The NIC@PLGA-HAs killed C. difficile vegetative cells at a minimum inhibitory concentration (MIC) of 4 μg/mL. When C. difficile cells were treated with NIC@PLGA-HAs at the 1/4 MIC, spore germination and biofilm formation were significantly inhibited compared to those in untreated cells (P < 0.01). NIC was found to interact with the receptor-binding domain of TcdB at 24 amino acid sites via an enthalpy-driven reaction (enthalpy change, 36.21 kJ/mol and entropy change, 212.9 J⋅mol/K). In vivo experimental findings in Mongolian gerbils indicated that NIC@PLGA-HAs outperformed free NIC in reducing pathological damage, diarrhea severity, weight loss, and TcdB production and enhanced the survival rate.Conclusion: These findings presented the therapeutic potential of NIC@PLGA-HAs with high solubility and stability, which simultaneously exerted multiple biological activities against C. difficile.
Sensors integrated with sampling and analysis processes are the key in analytical chemistry , environmental protection and national security. However, achieving reliable and sensitive large-scale rapid screening of target analytes is still challenging. Herein, we demonstrate a robust surface-enhanced Raman scattering (SERS) sensor by constructing dense and uniform plasmonic hotspots on the flexible Ti 3 C 2 Tx MXene/graphene oxide (MG) fibers through a self-assemble strategy at the oil-water interface. The produced SERS substrates exhibited an ultralow limit of detection (LOD, 1 ×10 −15 M for R6G), outstanding sensitivity (EF = 1.53 ×10 12 ) and high stability for R6G molecules (RSD = 9.47%, over 60 days storage). SERS experiments and theoretical simulations suggested that acidified Ti 3 C 2 Tx MXene further excited charge-transfer (CT) resonance of the system, while the assembled Ag nanostructures produced a large electromagnetic (EM) field enhancement. Thus, the fiber sensor not only realizes the multiplexed and powerful detection of pesticide residues (LOD of 10 −11 M) with an error < 7.3% via an established concentration-dependent standard color barcodes, but also allows the recognization of target molecules in a wide range of fields, such as methylene blue , crystal violet and nikethamide. This work provides new insights in the development of versatile label-free sensors for the rapid multiplexed analysis of target molecules in real samples.
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