Matairesinol 纳米颗粒在临床前模型中恢复化学敏感性并抑制结直肠癌进展：脂质代谢重编程的作用,Nano Letters

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Matairesinol 纳米颗粒在临床前模型中恢复化学敏感性并抑制结直肠癌进展：脂质代谢重编程的作用
Nano Letters ( IF 9.6 ) Pub Date : 2023-02-20 , DOI: 10.1021/acs.nanolett.3c00035
Shenshen Wu ₁ , Jiajia Wang ₁ , Zan Fu ₂ , Giuseppe Familiari ₃ , Michela Relucenti ₄ , Michael Aschner ₅ , Xiaobo Li _{1,

6} , Hanqing Chen ₇ , Rui Chen _{1,

8,

9,

10}

Affiliation

School of Public Health, Capital Medical University, Beijing 100069, P.R. China.
Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, P.R. China.
Department of Anatomical, Histological, Medical and Legal Locomotive Apparatus, Section of Human Anatomy Via Alfonso Borelli, Sapienza University of Rome, Roma 5000161, Italia.
Department of Anatomical, Histological, Forensic Medicine and Orthopedic Science, Sapienza University of Rome, Roma 5000161, Italia.
Department of Molecular Pharmacology, Albert Einstein College of Medicine, Forchheimer 209, 1300 Morris Park Avenue, Bronx, New York 10461, United States.
Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing 210009, P.R. China.
Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou 510180, P.R. China.
Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing 100069, P. R. China.
Beijing Laboratory of Allergic Diseases, Capital Medical University, Beijing 100069, P.R. China.
Institute for Chemical Carcinogenesis, Guangzhou Medical University, Guangzhou 511436, P.R. China.

致癌驱动的脂肪生成代谢是结直肠癌 (CRC) 进展的常见标志。因此，迫切需要开发新的代谢重编程治疗策略。在此，使用代谢组学分析比较了 CRC 患者和配对的健康对照之间血浆中的代谢特征。马泰尔素下调在 CRC 患者中很明显，补充马泰尔素可显着抑制偶氮甲烷/葡聚糖硫酸钠 (AOM/DSS) 结肠炎相关 CRC 小鼠的 CRC 肿瘤发生。Matairesinol 通过诱导线粒体损伤和氧化损伤以及抑制 ATP 的产生来重新连接脂质代谢以提高 CRC 的治疗效果。最后，负载马塔瑞素的脂质体通过恢复对 FOLFOX 方案的化学敏感性，显着促进 5-Fu/亚叶酸联合奥沙利铂 (FOLFOX) 在 CDX 和 PDX 小鼠模型中增强的抗肿瘤活性。总的来说，我们的研究结果强调了马泰酚介导的脂质代谢重编程作为一种新的药物策略来恢复 CRC 化学敏感性，这种马泰酚的纳米化方法将提高化疗疗效并具有良好的生物安全性。

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Matairesinol Nanoparticles Restore Chemosensitivity and Suppress Colorectal Cancer Progression in Preclinical Models: Role of Lipid Metabolism Reprogramming

Oncogenic-driven lipogenic metabolism is a common hallmark of colorectal cancer (CRC) progression. Therefore, there is an urgent need to develop novel therapeutic strategies for metabolic reprogramming. Herein, the metabolic profiles in the plasma between CRC patients and paired healthy controls were compared using metabolomics assays. Matairesinol downregulation was evident in CRC patients, and matairesinol supplementation significantly represses CRC tumorigenesis in azoxymethane/dextran sulfate sodium (AOM/DSS) colitis-associated CRC mice. Matairesinol rewired lipid metabolism to improve the therapeutic efficacy in CRC by inducing mitochondrial damage and oxidative damage and blunting ATP production. Finally, matairesinol-loaded liposomes significantly promoted the enhanced antitumor activity of 5-Fu/leucovorin combined with oxaliplatin (FOLFOX) in CDX and PDX mouse models by restoring chemosensitivity to the FOLFOX regimen. Collectively our findings highlight matairesinol-mediated lipid metabolism reprogramming as a novel druggable strategy to restore CRC chemosensitivity, and this nanoenabled approach for matairesinol will improve the chemotherapeutic efficacy with good biosafety.

更新日期：2023-02-20

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