Cationic nanoparticles with disrupting neutrophil extracellular traps inhibit the progression of head and neck squamous cell carcinoma

作者：Zhaoqiang Zhang, Yujie Kang, LU Bing-xu, G. Zhang, Baohan Xie, Yunyi Wang · 发表于：Frontiers in Cell and Developmental Biology · 年份：2026 · DOI：10.3389/fcell.2026.1803439 · 被引用次数：1 · 研究领域：Neutrophil, Myeloperoxidase and Oxidative Mechanisms、Immune cells in cancer、Inflammatory Biomarkers in Disease Prognosis

Introduction Immune checkpoint inhibitors (ICIs) have demonstrated promising therapeutic potential in head and neck squamous cell carcinoma (HNSCC). However, their clinical efficacy remains limited due to low response rates, largely attributed to the highly immunosuppressive tumor microenvironment (TME). Neutrophil extracellular traps (NETs) have recently been implicated in tumor progression and immune regulation. Therefore, this study aims to investigate the role of NETs in the TME and metastasis of HNSCC, and then to utilize cationic nanoparticles (cNP) to efficiently disrupt NETs in order to improve the immunosuppressive TME and inhibit metastasis, thereby suppressing the progression of HNSCC. Methods Histological and bioinformatics analyses were performed to evaluate NET-related signatures in HNSCC tissues and their association with immune cell infiltration. In vitro (scratch, cell adhesion and cytoskeletal remodeling assay) and in vivo (flow cytometry, immunofluorescence staining) experiments were conducted to investigate the effects of cationic nanoparticles (cNP) on NETs disruption, tumor cell migration, therapeutic efficacy and modulation of the TME. The underlying mechanism by which NET-DNA promotes HNSCC cell migration via CCDC25 was assessed using multiple approaches. Specifically, histological and immunohistochemical staining, western blotting, transfection, qRT-PCR, and transwell assays were performed. Results Histological analysis revealed that the expression le...