温和温度光热疗法（mild PTT）通过缓解高温引起的健康组织损伤，是一种安全而有前途的肿瘤治疗方式。然而，它的治疗效率很容易受到热休克蛋白（HSPs）的限制。因此，利用抑制HSPs的创新方法增强温和PTT效率对于PTT的临床应用非常关键。因此，本文报道了一种创新的策略：基于Mn-gallate纳米制剂的pyroptosis-boosted mild PTT。纳米制剂通过没药酸（GA）和Mn2+的协同配合构建而成。其显示出酸激活降解和释放Mn2+和GA以促进活性氧（ROS）上调、线粒体功能障碍和细胞凋亡。ATP的降解和ROS积累为抑制HSPs的表达提供了强有力的途径，从而实现了纳米制剂介导的温和PTT。我们的体外和体内实验结果表明，这种pyroptosis辅助的PTT策略可以高效地治疗骨肉瘤。 ©2023作者或许可人。

Mild-temperature photothermal therapy (mild PTT) is a safe and promising tumor therapeutic modality by alleviating the damage of healthy tissues around the tumor due to high temperature. However, its therapeutic efficiency is easily restricted by heat shock proteins (HSPs). Thus, exploitation of innovative approaches of inhibiting HSPs to enhance mild PTT efficiency is crucial for the clinical application of PTT.Herein, an innovative strategy is reported: pyroptosis-boosted mild PTT based on a Mn-gallate nanoformulation. The nanoformulation was constructed via the coordination of gallic acid (GA) and Mn2+. It shows an acid-activated degradation and releases the Mn2+ and GA for up-regulation of reactive oxygen species (ROS), mitochondrial dysfunction and pyroptosis, which can result in cellular ATP deprivation via both the inhibiton of ATP generation and incresed ATP efflux. The reduction of ATP and accumulation of ROS provide a powerful approach for inhibiting the expression of HSPs, which enables the nanoformulation-mediated mild PTT.Our in-vitro and in-vivo results demonstrate that this strategy of pyroptosis-assited PTT can achieve efficient mild PTT efficiency for osteosarcoma therapy.© 2023. The Author(s).