光热疗法（PTT）作为一种高效的非侵入性治疗方法而受到关注。然而，其治疗所需的局部高温（>50°C）不可避免地会对周围正常组织造成损害。因此，开发新颖有效的策略来实现温和光热疗法（mPTT）非常重要。热休克蛋白（HSP）是一种广泛存在的热应激蛋白，其过度表达导致癌细胞产生耐热性，严重影响治疗效果。因此，抑制HSPs的表达以降低肿瘤细胞的耐热性有望增强mPTT的治疗效果。在这里，我们成功合成了一种将两亲性多肽与花青染料结合的荧光探针，并通过自组装过程实现了阻断剂SB705498的物理封装。 SB705498 促进瞬时受体电位香草酸成员 1 (TRPV1) 通道阻断，可通过阻断钙的流入来抑制热休克转录因子 1 (HSF 1) 的易位，从而影响 HSP 的表达，从而有可能增强温和条件下的癌症热疗。此外，纳米颗粒使NIR-II荧光成像具有良好的稳定性和高光热转换效率（48.10%）。因此，本研究为NIR-II成像引导下实现精确mPTT（<45°C）提供了新的策略。意义声明：抑制癌症光热疗法（PTT）中热休克蛋白（HSP）的过度表达有望增强轻度光热疗法（mPTT）的治疗效果。在本研究中，我们合成了一种用两亲性多肽与花青染料结合的荧光探针，并通过自组装过程物理包裹了阻断剂SB705498。作为一种瞬时受体电位香草醛 1 (TRPV1) 通道阻断剂，SB705498 通过阻断钙离子内流来抑制热休克转录因子 1 (HSF1) 易位，从而通过抑制 HSP 的表达来提高 mPTT 功效。该纳米颗粒还能够实现 NIR-II 荧光成像，具有良好的稳定性和高光热转换效率（48.10%）。因此，这项研究为 NIR-II mPTT 提供了一种新策略。版权所有 © 2024。由 Elsevier Ltd 出版。

Photothermal therapy (PTT) has attracted attention as a highly effective non-invasive treatment method. However, the high localized temperatures (>50°C) required for its treatment will inevitably cause damage to the surrounding normal tissues. Therefore, it is important to develop novel and effective strategies to achieve mild photothermal therapy (mPTT). The overexpression of heat shock proteins (HSPs), a widespread heat stress protein, leads to the generation of heat resistance in cancer cells, which seriously affects the therapeutic effect. Thus, inhibiting the expression of HSPs to reduce the heat resistance of tumor cells is expected to enhance the therapeutic effect of mPTT. Here, we successfully synthesized a fluorescent probe bonded with an amphiphilic polypeptide to a cyanine dye and achieved physical encapsulation of the blocker SB705498 through a self-assembly process. SB705498 promotes transient receptor potential vanilloid member 1 (TRPV1) channel blockade that can inhibit the translocation of the heat shock transcription factor 1 (HSF 1) by blocking the influx of calcium and thus affecting the expression of HSPs, which has the potential to enhance the thermotherapy of cancer under mild conditions. In addition, the nanoparticles enabled NIR-II fluorescence imaging with good stability and high photothermal conversion efficiency (48.10%). Therefore, this study provides a new strategy for realizing precise mPTT(<45°C) guided by NIR-II imaging. STATEMENT OF SIGNIFICANCE: Inhibition of overexpression of heat shock proteins (HSPs) in cancer photothermal therapy (PTT) is expected to enhance the therapeutic effect of mild photothermal therapy (mPTT). In this study, we synthesized a fluorescent probe bonded to cyanine dyes with amphiphilic polypeptides and physically wrapped the blocker SB705498 through a self-assembly process. As a transient receptor potential vanillin 1 (TRPV1) channel blocker, SB705498 inhibits heat shock transcription factor 1 (HSF1) translocation by blocking calcium ion influx, thereby improving mPTT efficacy by inhibiting the expression of HSPs. The nanoparticles also enable NIR-II fluorescence imaging with good stability and high photothermal conversion efficiency (48.10%). Thus, this study provides a new strategy for NIR-II mPTT.Copyright © 2024. Published by Elsevier Ltd.