Self-propelled nanozyme motors for targeted therapy of radiation cystitis by disrupting the inflammation-cfDNA vicious cycle.

Radiation cystitis is a common complication of pelvic radiotherapy that significantly compromises clinical outcomes. A principal pathogenic factor is the accumulation of cell-free DNA (cfDNA) released from damaged cells, which promotes inflammatory cytokine production and disturbs tissue homeostasis. The study aims to engineer a self-propelled nanozyme motor that clears cfDNA and restores redox balance as a dual-mechanistic therapy for radiation cystitis. The system operated using endogenous urea, a naturally abundant metabolite present in bladder urine, enabling sustained and coordinated autonomous propulsion following intravesical instillation. This mobility facilitated extensive mucosal coverage and deeper penetration, allowing the motors to capture cfDNA deposited on the irradiated mucosal surface. The nanozyme core eliminated radiation-induced reactive oxygen species, resulting in a reduction of oxidative stress. These combined effects suppressed activation of the cGAS-STING signaling pathway and lowered the release of pro-inflammatory cytokines. Both in vitro and in vivo investigations verified the anti-inflammatory activity of this platform, indicating its translational relevance for radiation cystitis treatment.