Precursor-engineered oxygen-self-sufficient carbon dots for remodeling the infectious microenvironment toward enhanced sonodynamic therapy of bacterial meningitis

Sonodynamic therapy (SDT) offers a promising non-antibiotic strategy for intracranial bacterial infections, but its efficacy is limited by the blood–brain barrier (BBB), lesion hypoxia, and potential systemic toxicity of conventional sonosensitizers. Here, we develop multifunctional manganese-doped carbon dots (Mn-CDs) through precursor engineering by hydrothermally carbonizing methylene blue (MB, a sonosensitive moiety), manganese gluconate (a coordinated catalytic source), and dragon fruit powder (a biocompatible carbon matrix). This design integrates MB-derived sonosensitive motifs and Mn-related catalase (CAT)-like catalytic sites into an ultrasmall carbon framework. Mn-CDs efficiently decompose pathological hydrogen peroxide (H 2 O 2 ) into oxygen (O 2 ), thereby relieving hypoxia and fueling ultrasound-triggered SDT to generate singlet oxygen. The resulting oxidative stress disrupts bacterial membranes, impairs metabolic activity, and achieves 98% antibacterial efficiency against methicillin-resistant Staphylococcus aureus (MRSA) in vitro . Owing to their ultrasmall size (around 4.84 nm) and good Mn retention, Mn-CDs cross the BBB and efficiently accumulate in infected brain tissue with favorable biosafety. In an MRSA-induced meningitis mouse model, Mn-CDs-mediated SDT markedly reduces cerebral bacterial burden, attenuates neuroinflammation by regulating TNF-α and IL-10, decreases neuronal apoptosis, and improves behavioral recovery. This microenvironment-adaptive Mn-CDs platform provides an intelligent strategy for treating drug-resistant central nervous system infections.