Interferon-γ-responsive theranostic nanoplatform for adaptive antibacterial therapy

Developing intelligent theranostic strategies capable of real-time infection assessment and adaptive treatment remains a significant challenge in wound management. Here, we present a smart theranostic nanoplatform (Apt-Ag⁺-GNR) that integrates fluorescence-guided detection, real-time adaptive silver ion (Ag⁺) release, and photothermal therapy (PTT) for the precise treatment of infections. This system utilizes interferon-γ (IFN-γ), an inflammation-specific biomarker with high detection sensitivity (limit of detection: 26.7 pg mL^-1) as both a diagnostic indicator and a therapeutic trigger. Upon recognition of IFN-γ, the platform employs fluorescence resonance energy transfer -based detection to assess severity in real time. Concurrently, Ag⁺ is dynamically modulated in response to IFN-γ levels, enabling severity-specific treatment. For mild infections, characterized by low fluorescence intensity and low IFN-γ expression, the system releases limited Ag⁺ to eliminate bacteria while minimizing unnecessary intervention. For severe wound infection, characterized by high fluorescence signals and high IFN-γ levels, the platform combines Ag⁺ therapy with PTT to enhance bacterial eradication. In vivo studies confirm that Apt-Ag⁺-GNR enables precise therapeutic modulation, effectively preventing overtreatment-related tissue damage, accelerating wound healing, and reducing inflammation. Histological and immunofluorescence analyses further demonstrate improved tissue regeneration. This platform has established a broadly applicable framework for adaptive theranostic systems, offering translational potential in managing severe wound infection models and providing a basis for future applications in chronic ulcers, diabetic wounds, and implant-related infections.