A universal strategy to enhance photothermal conversion efficiency by regulating the molecular aggregation states for safe photothermal therapy of bacterial infections.

Photothermal therapy (PTT) has emerged as a promising approach for treating bacterial infections. However, achieving a high photothermal conversion efficiency (PCE) of photothermal agents (PTAs) remains a challenge. Such a problem is usually compensated by the use of a high-intensity laser, which inevitably causes tissue damage. Here, we present a universal strategy to enhance PCE by regulating the molecular aggregation states of PTAs within thermoresponsive nanogels. We demonstrate the effectiveness of this approach using aggregation-induced emission (AIE) and aggregation-caused quenching (ACQ) PTAs, showing significant enhancements in PCE without the need for intricate molecular modifications. Notably, the highest PCEs reach up to 80.9% and 64.4% for AIE-NG and ACQ-NG, respectively, which are nearly 2-fold of their self-aggregate counterparts. Moreover, we elucidate the mechanism underlying PCE enhancement, highlighting the role of strong intermolecular π-π interactions facilitated by nanogel-induced volume contraction. Furthermore, we validate the safety and efficacy of this strategy in in vitro and in vivo models of bacterial infections at safe laser power densities, demonstrating its potential for clinical translation. Our findings offer a straightforward, universal, and versatile method to improve PTT outcomes while minimizing cytotoxicity, paving the way for enhanced treatment of bacterial infections with safe PTT protocols.