研究动态
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糖酵解抑制用于三阴性乳腺癌的协同光疗。

Glycolysis inhibition for synergistic phototherapy of triple-negative breast cancer.

发表日期:2023 Nov 03
作者: Yuqian Fu, Tingjie Bai, Panpan Xue, Qi Chen, Weili Deng, Shuangqian Yan, Xuemei Zeng
来源: Cellular & Molecular Immunology

摘要:

光疗是一种治疗肿瘤的局部精准治疗技术。然而,光热疗法和光动力疗法的治疗效果不可避免地分别受到肿瘤微环境缺氧和高热诱导的热休克蛋白的影响。在此,我们发现甘露糖(一种葡萄糖类似物)可以通过抑制癌细胞的糖酵解并通过抑制细胞三磷酸腺苷(ATP)的生成来抑制热休克蛋白的表达来逆转肿瘤缺氧。接下来,我们使用同时​​负载吲哚菁绿(ICG)和甘露糖分子的脂质纳米颗粒(称为imLipo)用于肿瘤治疗。体外和体内实验均证明imLipo纳米平台通过单次近红外激光照射下的协同光疗具有显着的治疗效果。这项工作表明糖酵解抑制可以克服光疗的挑战。此外,imLipo的所有三个部分(甘露糖、ICG和脂质)均已获得临床批准,我们设计的纳米平台在未来的肿瘤治疗方面具有巨大的潜力。
Phototherapy is a local and precise therapeutic technique for tumor treatment. However, the therapeutic effects of photothermal and photodynamic therapies are inevitably encountered by hypoxia of the tumor microenvironment and heat shock protein induced by hyperthermia, respectively. Herein, we found that mannose, a glucose analog, could reverse tumor hypoxia by inhibiting glycolysis of cancer cells and suppressing the expression of heat shock protein through inhibiting cellular adenosine triphosphate (ATP) generation. Next, we used lipid nanoparticles simultaneously loaded with indocyanine green (ICG) and mannose molecules, named imLipo, for tumor therapy. Both in vitro and in vivo experiments evidenced that the imLipo nanoplatform has significant therapeutic efficacy through synergistic phototherapy under single near-infrared laser irradiation. This work shows that glycolysis inhibition can overcome the challenges of phototherapy. In addition, all three parts (mannose, ICG, and lipid) of imLipo are clinically approved and our designed nanoplatforms have great potential for future tumor treatment.