Tumor cytotoxicity and immunogenicity of a novel V-jet neon plasma source compared to the kINPen.

Tumor cytotoxicity and immunogenicity of a novel V-jet neon plasma source compared to the kINPen.
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DOI:
10.1038/s41598-020-80512-w
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发表时间:
2021-01-08
期刊:
影响因子:
4.6
通讯作者:
Bekeschus S
Bekeschus S
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Miebach L;Freund E;Horn S;Niessner F;Sagwal SK;von Woedtke T;Emmert S;Weltmann KD;Clemen R;Schmidt A;Gerling T;Bekeschus S

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最近的研究表明冷物理血浆在癌症治疗中的潜力。过多的血浆源性活性氧和活性氮(ROS/RNS)在引发癌细胞氧化应激后介导多种抗肿瘤作用。我们的目标是利用这一原理,利用新设计的双射流氖等离子体源(Vjet)治疗结直肠癌细胞。治疗时间依赖性ROS/RNS生成诱导三维肿瘤球体内氧化、生长迟缓和细胞死亡。在半体内模型TUM-CAM中,Vjet显著降低了血管化肿瘤的生长,但未观察到肿瘤细胞免疫原性或树突状细胞摄取的增加。相比之下,已知在体外、体内和患者中介导抗癌作用的氩驱动的单射流kINPen在球状体中产生的ROS/RNS更少,最终细胞死亡。然而,在TUM-CAM模型中,kINPen同样有效,并诱导免疫原性癌细胞死亡(ICD)标志物的表达增强,导致树突状细胞对kINPen的吞噬增加,而对Vjet等离子体处理的肿瘤细胞则没有作用。此外,根据DIN-SPEC 91315的要求对Vjet进行了表征。我们的研究结果强调了等离子体设备对癌细胞的特异性作用,以评估等离子体癌治疗的最佳放电。
Recent research indicated the potential of cold physical plasma in cancer therapy. The plethora of plasma-derived reactive oxygen and nitrogen species (ROS/RNS) mediate diverse antitumor effects after eliciting oxidative stress in cancer cells. We aimed at exploiting this principle using a newly designed dual-jet neon plasma source (Vjet) to treat colorectal cancer cells. A treatment time-dependent ROS/RNS generation induced oxidation, growth retardation, and cell death within 3D tumor spheroids were found. In TUM-CAM, a semi in vivo model, the Vjet markedly reduced vascularized tumors' growth, but an increase of tumor cell immunogenicity or uptake by dendritic cells was not observed. By comparison, the argon-driven single jet kINPen, known to mediate anticancer effects in vitro, in vivo, and in patients, generated less ROS/RNS and terminal cell death in spheroids. In the TUM-CAM model, however, the kINPen was equivalently effective and induced a stronger expression of immunogenic cancer cell death (ICD) markers, leading to increased phagocytosis of kINPen but not Vjet plasma-treated tumor cells by dendritic cells. Moreover, the Vjet was characterized according to the requirements of the DIN-SPEC 91315. Our results highlight the plasma device-specific action on cancer cells for evaluating optimal discharges for plasma cancer treatment.
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