Photoactivatable peroxynitrite (ONOO−), with prolonged half-life, enhanced diffusion, and precise spatiotemporal control, has emerged as a potent anti-biofilm and antimicrobial agent. However, conventional ONOO− generators are usually designed using planar molecular skeletons, which suffer from aggregate-caused reactive oxygen species reduction, thereby restricting ONOO− production. Herein, we present the series of photoactivatable ONOO− generators with aggregation-induced emission (AIE) characteristics—PyTP-NO, PyPTP-NO, and +PyPTP-NO—among which +PyPTP-NO enables efficient ONOO− production. Enhancing electron-withdrawing capability and extending π-conjugation has proven to be an effective strategy for designing ONOO−-generating AIEgens, as the resulting increases in excitation coefficients and intersystem crossing promote both superoxide anion generation and nitric oxide (NO) release, thereby boosting ONOO− production. To overcome the biofilm barrier, +PyPTP-NO was further incorporated into the fast-dissolving tips of a bilayer microneedle patch (+PyPTP-NO@DMN) to enable rapid release of the +PyPTP-NO for efficient biofilm eradication, while the base layer was loaded with recombinant collagen (CF-1552) to facilitate wound healing. Post-activation, +PyPTP-NO converts to the non-toxic product +PyPTP-NH, minimizing photo-toxicity to ensure biosafety during wound healing. This study not only provides a generalizable molecular design strategy for developing efficient ONOO− generators but also establishes a versatile therapeutic platform that enables effective biofilm eradication and safe tissue regeneration.
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2025 The Author(s). Aggregate published by SCUT, AIEI, and John Wiley & Sons Australia, Ltd.
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