Snake-fangs-bioinspired intelligently-responsive two-stage AIE gen-containing microneedle-based platform for integrated photodynamic infected-wound management and visual therapeutic diagnosis.

Abstract

The efficient treatment of prevalent drug-resistant (DR) bacteria-infected wounds caused by the clinical use of conventional antibiotics remains a significant challenge. Here, a well-integrated intelligent drug-releasing, photodynamic therapy, and visual therapeutic diagnosis strategy combining burgeoning aggregation-induced emission luminogen (AIE-gen) and microneedling technology is innovatively proposed for advanced infected-wound management. This strategy is based on an intelligently responsive two-stage AIE-gen-containing microneedle-based platform (AIE-film/TS-MN) with a double-layer structure. The uppermost layer comprises an on-demand pH-responsive AIE-photosensitizer (AFPP)-based film (AIE-film). This layer is designed to achieve the precise release of reactive oxygen species (ROS) or nitrocefin, which responds to <i>β</i>-lactamase in DR bacteria. The basal layer is a two-stage microneedle (TS-MN) patch with a "core-shell" structure bio-inspired by snake fangs, providing outstanding anti-migratory origins and acid-responsive drug-releasing properties through crustaceous gelatin loaded with Fe-carbenicillin frameworks (Fe-MOF). AFPP and nitrocefin in AIE-film accurately respond to acidic wound-microenvironment and <i>β</i>-lactamase, colorfully changing from yellow and green to orange and red, respectively. This indicates that AIE-film/TS-MN exhibits significant potential as a novel biosensor to record the color-change semiquantitatively at wound-sites through smartphone analysis, visually achieving significantly infected wound-diagnosis/-assessment to facilitate the therapeutic efficacy. Additionally, the smart multiple drug-releasing synergistically eliminates DR-bacteria, including carbenicillin from Fe-MOF and AFPP-activating ROS. Comprehensive <i>in vitro</i> and <i>in vivo</i> experiments confirm that the telemedicine AIE-film/TS-MN offers advanced integrated therapeutic effects for active infected wound management. Additionally, it reduces antibiotic abuse and provides an innovative and promising strategy for visual medical diagnostics and therapeutic interventions.