Silver sodium nitroprusside nano-aggregates for ultrasound-activated immunomodulatory therapy of MRSA pneumonia.

The clinical management of methicillin-resistant Staphylococcus aureus (MRSA) pneumonia is hindered by biofilm infections and cytokine storms. A key challenge is the lack of real-time monitoring tools for the inflammatory microenvironment during treatment. In this study, we developed a theranostic platform (CS@EAgNP) using TPP-modified chitosan to load silver sodium nitroprusside nano-aggregates (AgNP) and epigallocatechin gallate (EGCG). This system combines ultrasound imaging with ultrasound-activated therapy. The CS@EAgNP nanoparticles can act as an excellent ultrasound contrast enhancer. In vivo ultrasound imaging indicated that AgNP generated significantly enhanced echo signals at the infection site, providing real-time and highcontrast visualization of the inflammatory foci that was unattainable with normal lung tissue.Moreover, these nanoparticles release NO, silver and EGCG under ultrasound. The NO and silver penetrate biofilms to kill MRSA, while EGCG scavenges ROS and modulates inflammation. This reduces pro-inflammatory cytokines like IL-6 and TNF-α, mitigating the cytokine storm. In vivo results further confirm that this image-guided strategy achieves significant bacterial clearance and promotes lung tissue regeneration without detectable toxicity to major organs. This integrated approach bridges diagnosis and treatment, offering a promising solution for managing MRSA pneumonia.