Ultrasound activatable microneedles for bilaterally augmented sono-chemodynamic and sonothermal antibacterial therapy.

Abstract

Chemodynamic therapy (CDT) employs Fenton catalysts to kill bacteria by converting hydrogen peroxide (H₂O₂) into toxic hydroxyl radical (•OH). Among them, Fenton-type metal peroxide nanoparticles fascinate nanomaterials with intriguing physiochemical properties, but research on this antibacterial agent is still in its infancy. Herein, a distinct CuO₂/TiO₂ heterostructure constituted of ultrasmall copper peroxide (CuO₂) nanoclusters and sonosensitized ultrathin oxygen vacancy-rich porous titanium oxide (OV-TiO₂) nanosheets was developed and was incorporated into microneedles for bilaterally augmented sono-chemodynamic and sonothermal antibacterial therapy. Engineering CuO₂ nanoclusters on the surface of TiO₂ nanosheets not only endows the Fenton catalytic activity for sono-chemodynamic therapy (SCDT), but also improves the sonodynamic and sonothermal performance of TiO₂ by narrowing the bandgap of TiO₂ and suppressing the recombination of electron-hole pairs. The high efficacy of this CuO₂/TiO₂ integrated microneedle (CTMN) patch was systematically demonstrated both in vitro and in vivo with the eliminating rate >99.9999% against multidrug resistant (MDR) pathogens in 5 min as well as accelerated wound tissue healing. This work highlights a promisingly new and efficient strategy for the development of sonosensitive and chemoreactive nanomedicine for non-antibiotic therapies. STATEMENT OF SIGNIFICANCE: Feton-type metal peroxides, a novel nanomaterial with self-supplied oxygen and hydrogen peroxide, can achieve effective antimicrobial activity in vitro. However, there is a lack of effective nanomaterial delivery systems and suitable means for in vivo activation/enhancement of antimicrobial activity during bacterial infected skin wound treatment. In this study, we designed and prepared efficient ultrasound activable microneedles that effectively addressed the deficiencies mentioned above and established a new paradigm for efficient utilization of metal peroxide nanomaterials and ultrasound based strategies. Noticeably, copper peroxide nanoclusters/oxygen vacancy-rich porous titanium oxide nanosheets (CuO₂/TiO₂) integrated microneedle (CTMN) patch combines advantages of both sono-chemodynamic and sonothermal antibacterial therapy, achieving one of the most instant and effective antibacterial efficacy (>99.9999% in 5 min) in vivo reported till now.