开发旨在消除光热治疗过程中基于热休克蛋白（HSP）的恶性肿瘤保护机制的多组分纳米药物仍然存在一个重大障碍。在此，利用明确的聚乙二醇化磷脂胶束来共封装槲皮素（QUE，一种天然抗癌剂和有效的 HSP 抑制剂）和吲哚青绿（ICG，一种光热剂），以实现同步和协同的药物作用。随后的研究证实，定制的胶束系统有效增强了 QUE 的水溶性并提高了其细胞内化效率。有趣的是，组成的聚乙二醇化磷脂诱导了异常的内质网应激，从而使肿瘤细胞对 QUE 敏感。此外，QUE 在抑制应激诱导的 HSP70 过度表达方面发挥着至关重要的作用，从而增强了 ICG 的光热功效。在全身应用中，所提出的纳米治疗药物在808 nm近红外照射下表现出在肿瘤内优先积聚，并对4T1异种移植肿瘤发挥显着的杀肿瘤作用，这得益于显着的近红外荧光成像引导的化学光热疗法。因此，我们制造多组分纳米药物的策略成为优化抗肿瘤治疗功效的协调平台，并为不同的治疗方式提供了宝贵的见解。

A significant impediment persists in developing multicomponent nanomedicines designed to dismantle the heat shock protein (HSP)-based protective mechanism of malignant tumors during photothermal therapy. Herein, well-defined PEGylated phospholipid micelles were utilized to coencapsulate quercetin (QUE, a natural anticancer agent and potent HSP inhibitor) and indocyanine green (ICG, a photothermal agent) with the aim of achieving synchronized and synergistic drug effects. The subsequent investigations validated that the tailored micellar system effectively enhanced QUE's water solubility and augmented its cellular internalization efficiency. Intriguingly, the compositional PEGylated phospholipids induced extraordinary endoplasmic reticulum stress, thereby sensitizing the tumor cells to QUE. Furthermore, QUE played a crucial role in inhibiting the stress-induced overexpression of HSP70, thereby augmenting the photothermal efficacy of ICG. In systemic applications, the proposed nanotherapeutics exhibited preferential accumulation within tumors and exerted notable tumoricidal effects against 4T1 xenograft tumors under 808 nm near-infrared irradiation, facilitated by prominent near-infrared fluorescence imaging-guided chemo-photothermal therapy. Therefore, our strategy for fabricating multicomponent nanomedicines emerges as a coordinated platform for optimizing antitumor therapeutic efficacy and offers valuable insights for diverse therapeutic modalities.