A self-regulated phototheranostic nanosystem with single wavelength-triggered energy switching and oxygen supply for multimodal synergistic therapy of bacterial biofilm infections

The exploration of antibiotic-independent phototherapy strategies for the treatment of bacterial biofilm infections has gained significant attention. However, efficient eradication of bacterial biofilms remains a challenge. Herein, a self-regulated phototheranostic nanosystem with single wavelength-triggered photothermal therapy (PTT)/photodynamic therapy (PDT) transformation and oxygen supply for multimodal synergistic therapy of bacterial biofilm infections is presented. This approach combines a eutectic mixture of natural phase-change materials (PCMs) and an aggregation-induced emission (AIE) phototheranostic agent TPA-ICN to form colloidally stable nanopartcicles (i.e. AIE@PCM NPs). The reversible solid−liquid phase transition of PCMs facilitates the adaptive regulation of the aggregation states of TPA-ICN, enabling a switch between the energy dissipation pathways for enhanced PDT in solid PCMs or enhanced PTT in liquid PCMs. Additionally, oxygen-carrying thermoresponsive nanoparticles are also introduced to alleviate the hypoxic microenvironment of biofilms by releasing oxygen upon heating by AIE@PCM NPs with enhanced PTT. The nanosystem exhibits outstanding therapeutic efficacy against bacterial biofilms both in vitro and in vivo, with an antibacterial efficiency of 99.99%. This study utilizes a self-regulated theranostic nanoplatform with adaptive PTT/PDT transformation via the phase transition of PCMs and heat-triggered oxygen release, holding great promise in the safe and efficient treatment of bacterial biofilm infections.