Synergistic quorum sensing inhibition and mild-temperature photothermal therapy of integrated nanoplatform for implant-associated biofilm infections

Abstract

In current clinical practice, the presence of biofilms poses a significant challenge in the effective elimination of bacterial infections because of the physical and chemical barriers formed by biofilms, which offer persistent protection to bacteria. Here, we developed hollow mesoporous polydopamine (hMP) nanoparticles (NPs) loaded with luteolin (Lu) as a quorum sensing inhibitor, which were further coated with hyaluronic acid (HA) shells to create hMP-Lu@HA NPs. We observed that upon reaching the infection site, the HA shells underwent initial degradation by the hyaluronidase enzyme present in the bacterial infection's microenvironment to expose the hMP-Lu NPs. Subsequently, Lu was released in response to the acidic conditions characteristic of bacterial infections, which effectively hindered and dispersed the biofilm. Moreover, when subjected to near-infrared irradiation, the robust photothermal conversion effect of hMP NPs accelerated the release of Lu and disrupted the integrity of the biofilms by localized heating. This dual action enhanced the eradication of the biofilm infection. Importantly, hMP-Lu@HA NPs also promoted tissue regeneration and healing at the implantation site, concurrently addressing biofilm infection. Taken together, this nanosystem, combined with mild-temperature photothermal therapy and quorum sensing inhibition strategy, holds significant potential for applications in the treatment of implantation-associated infections.