Peng Shengjie, Feng Yue, Yu K N, Wu Lijun, Chen Guodong, Yang Miaomiao, Zhao Lele, Cao Wei, Cui Qianwen, Chen Lianjun, Li Quan, Huang Yifan, Cheng Cheng, Zhu Fengqin, Han Wei
Anhui Province Key Laboratory of Medical Physics and Technology, Institute of Health and Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, 230031, P. R. China.
University of Science and Technology of China, Hefei, 230026, P. R. China.
Adv Sci (Weinh). 2024 Dec;11(46):e2401842. doi: 10.1002/advs.202401842. Epub 2024 Oct 23.
Despite the promise of cold atmospheric plasma (CAP) for cancer treatment, the challenges associated with the treatment of solid tumors and penetration depth limitations remain, restricting its clinical application. Here, biological evidence is provided that the killing effect of CAP treatment is confined to less than 500 µm subcutaneously and the actual biological dose decreased gradually with depth for the first time, indicating that the limited penetration depth has become an urgent problem that demands immediate solutions. Significantly, it is showed that different from high-dose treatments, CAP decreased the doses to the low-dose range but still exhibited anti-tumor effects via mitotic catastrophe. Unlike radiotherapy or chemotherapy, low-dose CAP treatment induces mitochondrial structural damage and dysfunction, disrupts energy metabolism and redox balance, and results in mitotic catastrophe. Collectively, these findings suggest that better understanding and taking full advantage of the dose-response gradient effect of CAP is a potential strategy to prompt its clinical application beyond improving CAP penetration.
尽管冷大气等离子体（CAP）在癌症治疗方面前景广阔，但与实体瘤治疗相关的挑战以及穿透深度限制仍然存在，这限制了其临床应用。在此，首次提供了生物学证据，表明CAP治疗的杀伤效果局限于皮下小于500微米的范围，且实际生物剂量随深度逐渐降低，这表明有限的穿透深度已成为亟待解决的紧迫问题。值得注意的是，研究表明，与高剂量治疗不同，CAP将剂量降低至低剂量范围，但仍通过有丝分裂灾难表现出抗肿瘤作用。与放疗或化疗不同，低剂量CAP治疗会诱导线粒体结构损伤和功能障碍，破坏能量代谢和氧化还原平衡，并导致有丝分裂灾难。总体而言，这些发现表明，更好地理解并充分利用CAP的剂量反应梯度效应是推动其临床应用的潜在策略，而不仅仅是提高CAP的穿透性。
