Background/Objectives: Despite the numerous advances in glioblastoma multiforme (GBM) treatment, GBM remains as the most malignant and aggressive form of brain cancer, characterized by a very poor outcome, highlighting the ongoing need for the development of new therapeutic strategies. A novel intervention using plasma-assisted local delivery of oncology drugs was developed to mediate the drug delivery, which might improve drug uptake and/or chemotherapeutic action. Topotecan (TPT), a water-soluble topoisomerase I inhibitor with major cytotoxic effects during the S-phase of the cell cycle, was selected as the candidate drug because despite its potent antitumor activity, the systemic administration to the brain is limited due to low crossing of the blood-brain barrier. For these reasons, TPT may be repurposed for local combined therapies. Methods: We aimed to explore options for the local treatment of GBM where systematic delivery is challenging, using a combination between plasma-based technologies and TPT on a human brain cancer cell line (U-251mg). Results: The evaluation of direct TPT plasma deposition using a helium plasma jet (J-Plasma, Apyx Medical) with a nebulizer onto U-251mg cells grown in 2D or 3D culture showed a reduction in the metabolic activity and cell mass and decreased long-term survival, indicating synergistic effects between the drug and the plasma treatment. The plasma-assisted approach was confirmed using temozolomide (TMZ) as a standard drug for glioblastoma treatment, as well as with two skin cancer cell lines. Conclusions: These results revealed a pathway for new combinations and approaches to local drug application for a range of cancers.
背景/目的：尽管多形性胶质母细胞瘤（GBM）的治疗已取得诸多进展，但其仍是最具恶性与侵袭性的脑癌类型，预后极差，这凸显了开发新型治疗策略的持续需求。本研究开发了一种利用等离子体辅助局部递送肿瘤药物的新型干预手段，旨在介导药物递送过程，可能提升药物摄取效率和/或化疗效果。拓扑替康（TPT）作为一种水溶性拓扑异构酶I抑制剂，在细胞周期S期具有显著细胞毒性效应，被选为候选药物。尽管其抗肿瘤活性强，但由于难以穿透血脑屏障，全身给药对脑部治疗效果有限。因此，TPT可能被重新定位用于局部联合治疗。方法：本研究旨在探索针对系统性给药困难的GBM局部治疗方案，通过将等离子体技术与TPT联合应用于人脑癌细胞系（U-251mg）。结果：使用配备雾化器的氦等离子体射流（J-Plasma，Apyx Medical）对二维或三维培养的U-251mg细胞进行直接TPT等离子体沉积评估，结果显示细胞代谢活性与细胞质量降低，长期存活率下降，表明药物与等离子体处理间存在协同效应。该等离子体辅助方法的有效性在使用胶质母细胞瘤标准治疗药物替莫唑胺（TMZ）及两种皮肤癌细胞系的实验中得到了进一步验证。结论：这些结果为多种癌症的局部药物应用开辟了新的联合治疗方案与技术路径。
肿瘤(癌症)患者之家