Inhibiting the formation of neutrophil extracellular traps to prevent the recurrence of post-operative glioblastoma
Yaobao Han, Mengxiao Han, Tingting Wang, Hao Zhang, Hanghang Liu, Yanhui Zheng, Jun Dong, Zhen Li
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. Surgical resection of GBM tumor still result in high rates of post-operative recurrence and mortality. Here this group evaluates the role of neutrophil extracellular traps (NETs) in GBM progression in both mice and patients, and reports NET-related mechanism to promote the proliferation and migration of residual tumor cells.