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.

中文翻译：

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通过调节分子聚集状态来提高光热转换效率的通用策略，用于细菌感染的安全光热治疗

光热疗法（PTT）已成为治疗细菌感染的一种有前景的方法。然而，实现光热剂（PTA）的高光热转换效率（PCE）仍然是一个挑战。这种问题通常可以通过使用高强度激光来弥补，但这不可避免地会造成组织损伤。在这里，我们提出了一种通过调节热响应纳米凝胶内 PTA 的分子聚集状态来增强 PCE 的通用策略。我们使用聚集诱导发射 (AIE) 和聚集引起猝灭 (ACQ) PTA 证明了这种方法的有效性，显示出 PCE 的显着增强，而不需要复杂的分子修饰。值得注意的是，AIE-NG 和 ACQ-NG 的最高 PCE 分别达到 80.9% 和 64.4%，几乎是自聚合对应物的 2 倍。此外，我们阐明了 PCE 增强的机制，强调了纳米凝胶诱导的体积收缩促进的强分子间 π−π 相互作用的作用。此外，我们在安全激光功率密度下的细菌感染体外和体内模型中验证了该策略的安全性和有效性，证明了其临床转化的潜力。我们的研究结果提供了一种简单、通用且多功能的方法来改善 PTT 结果，同时最大限度地减少细胞毒性，为通过安全的 PTT 方案加强细菌感染的治疗铺平了道路。