A fever-mimic response capable of recruiting reprogrammed macrophages holds great potential in the engineering of the tumor microenvironment (TME). Low-temperature photothermal therapy (LT-PTT) can maintain tumors at a fever-like temperature (<45 °C) temporarily; however, it still faces several challenges in efficient regulation of TME because of reciprocal cross-talk between the bypass pathways. Here, we report a synergistic engineering of TME through an enhanced activation of a fever-mimic response based on both LT-PTT and tumor vascular normalization. Such engineering is achieved by a fever-inducible lipid nanocomposite (GNR-T/CM-L), which produces mild heat (∼43 °C) and sequentially releases multicomponents to cooperatively upregulate interferon-gamma under NIR irradiation, forming a bidirectionally closed loop for downstream M1 tumor-associated macrophage polarization and promoting the inhibition of the tumor growth. In proof-of-concept studies, GNR-T/CM-L demonstrated efficient tumor ablation in breast tumor xenograft-bearing mice and significantly prolonged their survival period. It paves an avenue to precisely reprogram TME for efficient cancer therapy through synergistic pathways of creating fever-like responses in the tumor.

中文翻译：

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通过肿瘤微环境的协同工程促进癌症治疗的发热诱导脂质纳米复合材料。

能够募集重新编程的巨噬细胞的发烧模拟反应在肿瘤微环境（TME）的工程设计中具有巨大潜力。低温光热疗法（LT-PTT）可将肿瘤暂时维持在发烧样温度（<45°C）下；然而，由于旁路途径之间的相互串扰，在有效调节TME方面仍然面临一些挑战。在这里，我们报告通过基于LT-PTT和肿瘤血管正常化的发烧模拟反应的增强激活来实现TME的协同工程。这种工程化是通过发烧诱导的脂质纳米复合材料（GNR-T / CM-L）实现的，该复合物会产生适度的热量（约43°C），并在NIR辐射下依次释放多组分以协同上调干扰素-γ，形成下游M1肿瘤相关巨噬细胞极化的双向闭合环，并促进肿瘤生长的抑制。在概念验证研究中，GNR-T / CM-L证明了在荷瘤异种移植小鼠中有效的肿瘤消融，并显着延长了它们的生存期。它通过在肿瘤中产生发烧样反应的协同途径，精确地重新编程TME，以进行有效的癌症治疗。