Polysaccharides coated on mesoporous silica nanoparticles inhibit the inflammatory response for the treatment of sepsis.

To address the challenges of low antibiotic delivery efficiency and complex inflammatory microenvironments in sepsis therapy, we developed a multifunctional fluorescent nanoplatform, 1-PGA-2@MSN@Meropenem, for targeted drug delivery and hydrogen peroxide (H2O2)-responsive detection. This system employs mesoporous silica nanoparticles (MSN) as carriers, coated with polygalacturonic acid (PGA) for enhanced stability, and functionalized with a fluorescent small molecule (Compound 1) and a natural antimicrobial agent (Compound 2). Comprehensive characterization confirmed its mesoporous structure (average pore size ∼3.4 nm), large surface area (216.4 m2/g), and successful drug loading and surface modification (FT-IR, PXRD). Fluorescence analysis revealed a strong emission at 670 nm under 390 nm excitation with a large Stokes shift (>270 nm), offering excellent signal-to-noise ratio and imaging potential. The probe exhibited a linear fluorescence response to H2O2 over 0-40 μM (R2 = 0.9893), with a high association constant (Ka = 1.38 × 105 M-1) and outstanding selectivity. Furthermore, in an LPS-induced THP-1 macrophage inflammation model, the meropenem-loaded nanoparticles significantly downregulated pro-inflammatory cytokines TNF-α and IL-1β at the mRNA level, indicating their potential to mitigate sepsis-associated inflammation by suppressing macrophage-mediated immune responses. This work provides a promising strategy integrating drug delivery, biosensing, and immunomodulation for advanced sepsis management.