结直肠癌（CRC）的复发和转移一直被认为是临床治疗中的严重挑战。最近的研究表明，基质金属蛋白酶（MMPs）和乳酸可以促进局部肿瘤血管生成、复发和转移。MMPs的表达高度依赖于能量代谢，乳酸被认为是肿瘤增殖和转移的一种替代能源。因此，我们采用合理的方法设计了一种光热饥饿疗法纳米调节剂，可以降低能量代谢，抑制CRC的复发和转移。为了设计一种合适的纳米调节剂，我们通过共聚方法将葡萄糖氧化酶（GOX）、吲哚菁绿（IR820）和α-氰基-4-羟基肉桂酸（CHC）结合成纳米颗粒。IR820的光热特性提供了适当的温度和氧气供应，促进GOX的酶促反应，从而促进细胞内葡萄糖消耗。CHC抑制乳酸酸进入细胞的单羧酸转运蛋白1（MCT1）的表达，同时减少氧气消耗，促进GOX的反应。另外，通过改变三磷酸腺苷（ATP）合成以阻断热休克蛋白（HSPs）的表达，可以有效防止IR820介导的光热疗法耐药性。因此，这种双重光热饥饿疗法纳米调节剂通过耗尽细胞内营养物质有效抑制CRC的复发和转移。本文受版权保护，保留所有权利。

The recurrence and metastasis of colorectal cancer (CRC) have been considered as a severe challenge in clinical treatment. Recent studies have demonstrated that matrix metalloproteinases (MMPs) and lactate can promote local tumor angiogenesis, recurrence and metastasis. The expression of MMPs is highly dependent on energy metabolism, and lactate has been considered an alternative energy source for tumor proliferation and metastasis. Therefore, using a rational approach, we designed a photothermal-starvation therapy nanomodulator that can reduce energy metabolism to suppress CRC recurrence and metastasis. To design a suitable nanomodulator, we combine glucose oxidase (GOX), indocyanine green (IR820), and α-cyano-4-hydroxycinnamic acid (CHC) into nanoparticles by a co-assembly method. The photothermal properties of IR820 provide the appropriate temperature and oxygen supply for the enzymatic reaction of GOX to promote intracellular glucose consumption. CHC inhibits the expression of monocarboxylate transporter 1 (MCT1), the transporter of lactic acid into cells, and also reduces oxygen consumption and promotes the GOX reaction. Additionally, altering adenosine triphosphate (ATP) synthesis to block heat shock proteins (HSPs) expression can be an effective means to prevent IR820-mediated photothermal therapy resistance. Thus, this dual photothermal-starvation therapy nanomodulator efficiently suppresses the recurrence and metastasis of CRC by depleting intracellular nutrients. This article is protected by copyright. All rights reserved.This article is protected by copyright. All rights reserved.