Selenium nanoparticles as adjunctive therapy in sepsis: A pilot randomized clinical trial

Immunosuppression in sepsis often leads to treatment failure due to impaired host defense, underscoring an urgent need for novel therapeutic strategies to restore immune function. To address this challenge, we designed functional selenium nanoparticles (SeNPs) and conducted a pilot randomized clinical trial to evaluate the efficacy and safety of SeNPs in sepsis patients with immune dysfunction. The trial was registered with the Chinese Clinical Trial Registry (ChiCTR2300072222). Eligible patients were randomly assigned in 1:1 ratio to receive either standard care alone or standard care supplemented with SeNPs (400 μg selenium daily). The primary endpoint was immune function, assessed by lymphocyte counts and subsets on days 1, 4, 7, and 10 after randomization. Seventy patients were enrolled, and 68 completed the trial (34 per group). Compared with the control group, SeNPs supplementation was associated with improved immune function, reflected by higher total lymphocyte counts and increased absolute counts of CD3⁺ , CD4⁺, and CD8⁺ T cell subsets on days 4, 7, and 10. SeNPs supplementation was also associated with reduced inflammation, as indicated by lower levels of pro-inflammatory cytokines IL-6 and HMGB1. Furthermore, SeNPs supplementation demonstrated protective effects on multiple organ functions, decreased markers of systemic infection, and reduced intensive care unit and hospital mortality. No adverse events were reported during the study. These findings suggest that SeNPs supplementation enhances immune function, attenuates excessive inflammation, and protects against multiple organ dysfunctions with a favorable safety profile in patients with sepsis. Thus, SeNPs could serve as a promising adjunctive therapy for sepsis.