文章：

冷大气等离子体选择性靶向神经母细胞瘤：机制解析与体内验证

Cold Atmospheric Plasma Selectively Targets Neuroblastoma: Mechanistic Insights and In Vivo Validation

原文发布日期：25 October 2025

DOI: 10.3390/cancers17213432

类型: Article

开放获取: 是

英文摘要：

Background: Neuroblastoma (NB) presents significant challenges in pediatric oncology, particularly in high-risk cases where local recurrence occurs in ~35% of patients. Cold Atmospheric Plasma (CAP) has emerged as a promising treatment due to its selective cytotoxicity toward cancer cells while sparing normal cells. Methods: This study assessed CAP efficacy using in vitro NB cell lines (SK-N-AS and LAN-5) and in vivo xenograft murine models. In vitro, CAP was applied via a helium jet, and cellular responses were evaluated for viability, reactive oxygen species (ROS), lipid peroxidation, DNA damage, and cell cycle, while apoptosis was measured by Annexin V/PI flow cytometry. In vivo, CAP was applied to unresected tumors and residual tumors after incomplete resection. Tumor regrowth was monitored, and histological analysis was performed. Results: CAP reduced NB cell viability in a dose- and time-dependent manner by increasing intracellular ROS and lipid peroxidation. CAP-treated NB cells showed a 50% rise in oxidative DNA damage, a two-fold increase in apoptosis, and alterations in cell-cycle progression, while normal fibroblasts showed modest effects. CAP predominantly induced apoptosis, though secondary necrosis appeared with prolonged exposures, consistent with caspase-3 and PARP pathways. In xenografts, CAP reduced tumor diameter by 60% and increased caspase-3-positive cells, with minimal effects on normal tissue. Conclusions: CAP demonstrates strong therapeutic potential as a targeted, non-invasive NB treatment, particularly for residual tumors near vascular structures with consistent exposure times (60–300 s).

摘要翻译： 

背景：神经母细胞瘤（NB）是儿科肿瘤学领域面临的重大挑战，尤其在约35%的高危病例中会出现局部复发。冷大气压等离子体（CAP）因其对癌细胞具有选择性细胞毒性且不损伤正常细胞，已成为一种前景广阔的治疗手段。方法：本研究通过体外NB细胞系（SK-N-AS和LAN-5）和体内异种移植小鼠模型评估CAP疗效。体外实验中采用氦气射流施加CAP处理，通过检测细胞活力、活性氧（ROS）、脂质过氧化、DNA损伤和细胞周期评估细胞反应，同时采用膜联蛋白V/PI流式细胞术测定细胞凋亡。体内实验中，CAP被应用于未切除肿瘤及不完全切除后的残留肿瘤，监测肿瘤再生情况并进行组织学分析。结果：CAP通过增加细胞内ROS和脂质过氧化水平，以剂量和时间依赖性方式降低NB细胞活力。CAP处理的NB细胞氧化性DNA损伤增加50%，细胞凋亡率提升两倍，细胞周期进程发生改变，而正常成纤维细胞仅出现轻微影响。CAP主要诱导细胞凋亡，但长时间暴露会出现继发性坏死，这与caspase-3和PARP通路激活相一致。在异种移植模型中，CAP使肿瘤直径减少60%，caspase-3阳性细胞增加，且对正常组织影响极小。结论：CAP作为一种靶向、非侵入性的NB治疗手段展现出强大的治疗潜力，尤其适用于血管结构附近残留肿瘤的持续暴露治疗（60-300秒）。

原文链接：

Cold Atmospheric Plasma Selectively Targets Neuroblastoma: Mechanistic Insights and In Vivo Validation