尽管光热疗法（PTT）可以有效杀死肿瘤细胞，但它可能会无意中损害肿瘤周围的健康组织。然而，降低治疗温度会降低治疗效果。在这项研究中，我们采用了 2,2'-((2Z,2'Z)-((4,4,9,9-四己基-4,9-二氢-s-茚达烯基[1,2-b:5, 6-b']二噻吩-2,7-二基)双(亚甲基))双(3-氧代-2,3-二氢-1H-茚-2,1-二亚基))二丙二腈(IDIC)，一种具有传统的受体-供体-受体（A-D-A）结构，作为光热剂（PTA）以促进有效的温和光热疗法（mPTT）。 IDIC 在激光照射下促进分子内电荷转移，使其成为 mPTT 的有前途的候选者。为了增强IDIC的治疗潜力，我们将槲皮素（Qu）掺入IDIC中形成IDIC-Qu纳米颗粒（NPs），它可以抑制mPTT过程中的热休克蛋白（HSP）活性。此外，IDIC-Qu NPs 由于其增强的渗透和保留（EPR）效应而表现出优异的水分散性和对肿瘤组织的被动靶向能力。这些有利的特性使 IDIC-Qu NP 成为靶向肿瘤治疗的有希望的候选者。重要的是，IDIC-Qu NPs 表现出可控的光热效应，对癌细胞具有出色的体外细胞毒性，并通过 mPTT 有效体内肿瘤消融。 IDIC-Qu NPs 纳米系统丰富了有机 PTA 家族，并为 mPTT 的未来临床应用带来了巨大前景。版权所有 © 2024 Elsevier Inc. 保留所有权利。

Although photothermal therapy (PTT) is effective at killing tumor cells, it can inadvertently damage healthy tissues surrounding the tumor. Nevertheless, lowering the treatment temperature will reduce the therapeutic effectiveness. In this study, we employed 2,2'-((2Z,2'Z)-((4,4,9,9-Tetrahexyl-4,9-dihydro-s-indaceno[1,2-b:5,6-b']dithiophene-2,7-diyl)bis(methanylylidene))bis(3-oxo-2,3-dihydro-1H-indene-2,1-diylidene)) dimalononitrile (IDIC), a molecule possessing a conventional acceptor-donor-acceptor (A-D-A) structure, as a photothermal agent (PTA) to facilitate effective mild photothermal therapy (mPTT). IDIC promotes intramolecular charge transfer under laser irradiation, making it a promising candidate for mPTT. To enhance the therapeutic potential of IDIC, we incorporated quercetin (Qu) into IDIC to form IDIC-Qu nanoparticles (NPs), which can inhibit heat shock protein (HSP) activity during the process of mPTT. Moreover, IDIC-Qu NPs exhibited exceptional water dispersibility and passive targeting abilities towards tumor tissues, attributed to its enhanced permeation and retention (EPR) effect. These advantageous properties position IDIC-Qu NPs as a promising candidate for targeted tumor treatment. Importantly, the IDIC-Qu NPs demonstrated controllable photothermal effects, leading to outstanding in vitro cytotoxicity against cancer cells and effective in vivo tumor ablation through mPTT. IDIC-Qu NPs nano-system enriches the family of organic PTAs and holds significant promise for future clinical applications of mPTT.Copyright © 2024 Elsevier Inc. All rights reserved.