Work

Molecular Engineering of Aggregation‐induced Emission Peroxynitrite Generators for Biofilm Eradication via Bilayer Microneedles

Year: 2025

Type: article

Abstract: ABSTRACT 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.

Source: Aggregate

DOI: 10.1002/agt2.70181