抑制中性粒细胞胞外诱捕网的形成以预防术后胶质母细胞瘤的复发

抑制中性粒细胞胞外陷阱的形成以预防术后胶质母细胞瘤的复发

Inhibiting the formation of neutrophil extracellular traps to prevent the recurrence of post-operative glioblastoma

作者:Yaobao Han, Mengxiao Han, Tingting Wang, Hao Zhang, Hanghang Liu, Yanhui Zheng, Jun Dong, Zhen Li

期刊:Nature communications

摘要

胶质母细胞瘤（GBM）是一种高度恶性的肿瘤，具有较高的术后复发率。开发创新且有效的预防复发的方法具有重要意义。本文重点探讨中性粒细胞胞外陷阱（NETs）在小鼠及患者GBM进展中的关键作用。中性粒细胞在手术腔周围积聚并释放NETs，促进术后残存GBM细胞的增殖与迁移。将含铜硒纳米酶和多柔比星的水凝胶注入手术腔，成功抑制了NETs的形成，并显著提高了对GBM的治疗效果。接受治疗的GBM小鼠中，有60%的动物存活超过24个月，存活时间是未治疗组的36倍，接近健康小鼠的寿命。治疗组小鼠保持了其基本的认知功能和运动能力。该研究展示了调控NETs在GBM治疗中的巨大潜力。

Abstract

Glioblastoma (GBM) is a highly malignant tumor with a high postoperative recurrence rate. It is crucial to develop innovative and effective approaches to prevent its recurrence. Herein, we focus on the important roles of neutrophil extracellular traps (NETs) in the progression of GBM in mice and patients. Neutrophils accumulate around the surgical cavity and release NETs to promote the proliferation and migration of postoperative residual GBM cells. Injection of a hydrogel loaded with copper selenide nanozyme and doxorubicin into the surgical cavity successfully inhibit the formation of NETs and improve the therapeutic efficacy against GBM. 60% of treated GBM mice survive over 24 months, which are 36 times longer than those of untreated mice, and close to the lifespan of healthy mice. The treated mice preserve their essential cognitive functions and basic motor ability. This study demonstrates the great potential of modulating NETs in GBM therapy.

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