Jiang Kehua, Liu Hongming, Chen Xiaolong, Wang Zhen, Wang Xiaodong, Gu Xiaoya, Tong Yonghua, Ba Xiaozhuo, He Yu, Wu Jian, Deng Wen, Wang Qing, Tang Kun
Department of Urology, Guizhou Provincial People's Hospital, Guiyang, Guizhou, People's Republic of China.
Department of Urology, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, People's Republic of China.
Int J Nanomedicine. 2025 Apr 5;20:4201-4234. doi: 10.2147/IJN.S513207. eCollection 2025.
Although immunotherapy has made significant progress in cancer treatment, its limited responsiveness has greatly hindered widespread clinical application. The Warburg effect in tumor cells creates a tumor microenvironment (TME) characterized by hypoxia, low glucose levels, and high lactate levels, which severely inhibits the antitumor immune response. Consequently, targeting glucose metabolism to reprogram the TME is considered an effective strategy for reversing immunosuppression and immune evasion. Numerous studies have been conducted on enhancing cancer immunotherapy efficacy through the delivery of glucose metabolism modulators via nanocarriers. This review provides a comprehensive overview of the glucose metabolic characteristics of tumors and their impacts on the immune system, as well as nanodelivery strategies targeting glucose metabolism to enhance immunotherapy. These strategies include inhibiting key glycolytic enzymes, blocking glucose and lactate transporters, and utilizing glucose oxidase and lactate oxidase. Furthermore, this article reviews recent advancements in synergistic antitumor therapy involving glucose metabolism-targeted therapy combined with other treatments, such as chemotherapy, radiotherapy (RT), phototherapy, and immunotherapy. Finally, we discuss the limitations and future prospects of nanotechnology targeting glucose metabolism therapy, hoping to provide new directions and ideas to improve cancer immunotherapy.
尽管免疫疗法在癌症治疗方面取得了重大进展，但其有限的反应性极大地阻碍了其在临床上的广泛应用。肿瘤细胞中的瓦博格效应创造了一种以缺氧、低葡萄糖水平和高乳酸水平为特征的肿瘤微环境（TME），这严重抑制了抗肿瘤免疫反应。因此，靶向葡萄糖代谢以重新编程TME被认为是逆转免疫抑制和免疫逃逸的有效策略。已经进行了大量研究，通过纳米载体递送葡萄糖代谢调节剂来提高癌症免疫治疗的疗效。本综述全面概述了肿瘤的葡萄糖代谢特征及其对免疫系统的影响，以及靶向葡萄糖代谢以增强免疫治疗的纳米递送策略。这些策略包括抑制关键糖酵解酶、阻断葡萄糖和乳酸转运体，以及利用葡萄糖氧化酶和乳酸氧化酶。此外，本文综述了涉及葡萄糖代谢靶向治疗与其他治疗（如化疗、放疗（RT）、光疗和免疫治疗）联合的协同抗肿瘤治疗的最新进展。最后，我们讨论了靶向葡萄糖代谢治疗的纳米技术的局限性和未来前景，希望为改善癌症免疫治疗提供新的方向和思路。
