Carrier‐free nanodrugs that integrate chemodrugs and other therapeutic agents demonstrate good efficacy and minimized side effects, showing promise for combined therapy. However, a key challenge lies in enhancing the bioavailability and therapeutic potential of the nanodrugs through a controllable assembly process. Herein, a carrier‐free photothermal nanodrug (ZPQ NPs) is constructed through flavonol‐driven assembly with amine‐substituted perylene diimide for enhanced chemo‐photothermal combined cancer therapy. The flavonol, particularly quercetin, facilitates J‐aggregation of perylene diimide derivatives within the nanodrug and contributes to multiple improvements, including red‐shifted absorption, enhanced fluorescence intensity, improved photothermal conversion efficiency as well as excellent photostability. Moreover, the nanodrug also demonstrates enhanced cellular uptake and intracellular reactive oxygen species scavenging capability. The combination of quercetin and photothermal effect effectively kills cancer cells, as well as alleviates inflammation following photothermal therapy. Guided by in vivo fluorescence imaging, the application of ZPQ NPs results in complete tumor elimination and effectively inhibits tumor recurrence through chemo‐photothermal combined therapy. This work presents a straightforward strategy for constructing carrier‐free nanodrugs that exhibit simultaneous enhancements in both photophysical properties and biological activity.

中文翻译：

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通过黄酮醇驱动的组装增强无载体光热纳米药物


整合化疗药物和其他治疗药物的无载体纳米药物表现出良好的疗效和最小化的副作用，显示出联合治疗的前景。然而，一个关键的挑战在于通过可控的组装过程来提高纳米药物的生物利用度和治疗潜力。在此，通过黄酮醇驱动的胺取代苝二酰亚胺组装构建了一种无载体光热纳米药物（ZPQ NPs），用于增强化学光热联合癌症治疗。黄酮醇，特别是槲皮素，促进纳米药物内苝二酰亚胺衍生物的J聚集，并有助于多种改进，包括红移吸收、增强荧光强度、提高光热转换效率以及优异的光稳定性。此外，纳米药物还表现出增强的细胞摄取和细胞内活性氧清除能力。槲皮素和光热效应的结合可以有效杀死癌细胞，并减轻光热治疗后的炎症。在体内荧光成像引导下，ZPQ NPs的应用通过化学光热联合治疗实现了肿瘤的完全消除并有效抑制肿瘤复发。这项工作提出了一种构建无载体纳米药物的简单策略，该药物在光物理性质和生物活性方面同时增强。