Dual-function niobium-doped carbon dots for ferroptosis-driven anti-inflammatory therapy in pseudomonas aeruginosa pneumonia via GPX4 axis

Escalation of antimicrobial resistance (AMR) and the complex pathophysiology of severe hospital-acquired Pseudomonas aeruginosa (PA) pneumonia, driven by a vicious cycle of oxidation-inflammation and ferroptosis, require innovative therapeutic strategies beyond traditional antibiotics. Host-directed therapies that modulate immune responses and reduce tissue damage are promising. We developed niobium-doped Arctiin-derived carbon dots (Nb-Arctiin-CDs) via a one-step hydrothermal strategy. This nanoplatform integrates the intrinsic anti-inflammatory and antioxidant properties of Arctiin with the redox activity of niobium within a biocompatible carbon-based framework, enabling enhanced therapeutic functionality. Nb-Arctiin-CDs demonstrate strong antibacterial and biofilm-eradication effects against PA, killing over 90% of bacteria by disrupting membranes and inhibiting bacterial growth. In infected MHS cells, Nb-Arctiin-CDs suppressed inflammatory cytokine and iNOS expression, reduced oxidative stress, and restored mitochondrial membrane potential. Critically, the nanomaterial also acts as a potent ferroptosis inhibitor by coordinately downregulating ferroptosis drivers and restoring the core defense axis, with GPX4 serving as a regulator linking ferroptosis suppression to anti-inflammatory effects. In a mouse model of PA pneumonia, Nb-Arctiin-CDs decrease lung injury, edema, and cytokine levels while improving bacterial clearance. Biosafety analysis shows excellent biocompatibility and no systemic toxicity. Nb-Arctiin-CDs offer a safe, effective host-directed therapy with potential for treating bacterial pneumonia and ferroptosis-related inflammatory diseases.