生物矿化双酶纳米颗粒调控肿瘤糖代谢诱导肿瘤细胞焦亡及增强抗肿瘤免疫治疗

Biomineralized Two-Enzyme Nanoparticles Regulate Tumor Glycometabolism Inducing Tumor Cell Pyroptosis and Robust Antitumor Immunotherapy.

机构信息

Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, P. R. China.

University of Science and Technology of China, Hefei, 230026, P. R. China.

出版信息

Adv Mater. 2022 Dec;34(50):e2206851. doi: 10.1002/adma.202206851. Epub 2022 Nov 3.

Abstract

Currently, immune checkpoint therapy combined with chemotherapy and radiotherapy is a useful strategy for improving immunotherapy's therapeutic efficacy. However, chemotherapy and radiotherapy cause serious side effects, so finding safe and effective methods to combine with immunotherapy is critical. In this work, regulating tumor glycometabolism is found to induce tumor cell pyroptosis and regulate the degree of expression of programmed death-ligand 1 (PD-L1). Therefore, how to treat tumors by regulating tumor glycometabolism in combination with anti-PD-L1 therapy is investigated here. First, the biomineralization-like method is used to construct nanoparticles with two-enzymatic activity by hybridizing nanozymes and glucose oxidase (GOx). It has the ability to self-amplify regulation of the glycometabolism of tumor cells. It can also induce tumor cell pyroptosis and increase the expression of PD-L1 in tumor cells. To treat tumors, nanoparticles are further combined with anti-PD-L1, which substantially inhibits tumor development and significantly increases  the survival time of mice. Combination therapy also has a significant immunological memory effect, successfully preventing tumor recurrence and metastasis. This is thought to be the first study that combines tumor glycometabolism with immunocheckpoint blocking in cancer therapy. This innovative, safe, low-toxic, and highly effective anti-tumor strategy can have good prospects in clinical applications.

摘要

目前,免疫检查点疗法联合化疗和放疗是提高免疫疗法疗效的有效策略。然而,化疗和放疗会引起严重的副作用,因此寻找安全有效的方法与免疫疗法相结合至关重要。在这项工作中,发现调节肿瘤糖代谢可以诱导肿瘤细胞焦亡并调节程序性死亡配体 1(PD-L1)的表达程度。因此,在这里研究了如何通过调节肿瘤糖代谢与抗 PD-L1 治疗相结合来治疗肿瘤。首先,采用类生物矿化方法通过纳米酶和葡萄糖氧化酶(GOx)杂交构建具有两种酶活性的纳米粒子。它具有自我放大调节肿瘤细胞糖代谢的能力。它还可以诱导肿瘤细胞焦亡并增加肿瘤细胞中 PD-L1 的表达。为了治疗肿瘤,进一步将纳米粒子与抗 PD-L1 结合,这可显著抑制肿瘤的发展并显著延长小鼠的存活时间。联合治疗还具有显著的免疫记忆效应,成功地防止了肿瘤的复发和转移。这被认为是首次将肿瘤糖代谢与免疫检查点阻断结合用于癌症治疗的研究。这种创新、安全、低毒、高效的抗肿瘤策略在临床应用中具有良好的前景。

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