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Published on: February 16, 2015
Systemic remodeling of the glioblastoma microenvironment via plasma-induced vascular disruption and CSF-propelled
Yinan Chen1, Zuhao Luo2, Chao Zhang3
1Institute of Plasma Physics, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, 230031, China; University of Science and Technology of China, Hefei, 230026, China; Department of Neurosurgery, Centre for Leading Medicine and Advanced Technologies of IHM, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230001, China.
Abstract:
Cold atmospheric plasma (CAP) exhibits potent anti-tumor activity against glioblastoma in vitro, yet the in vivo therapeutic efficacy of CAP may be restricted by the limited direct penetration depth of CAP. In glioblastoma, effective drug delivery to tumor tissue is crucial to glioblastoma treatment. The complex tumor microenvironment (TME) of glioblastoma and the limited permeability of the blood-brain barrier (BBB) are major obstacles to drug delivery into tumor tissue. Through comprehensive in vitro and in vivo studies, we characterize a novel tripartite mechanism of CAP therapy that overcomes these limitations. Rather than the conventional penetration-limited mechanisms, the results reveal that CAP exerts its therapeutic effects via three distinct but synergistic pathways: BBB integrity modulation, exploitation of cerebrospinal fluid (CSF)-mediated ROS distribution to deep tumor regions, and tumor-endothelial paracrine signaling network activation. This multimodal action collectively overcomes glioblastoma TME barriers, establishing CAP as a systemic microenvironmental regulator rather than merely a local cytotoxic agent. These findings provide a transformative framework for clinical translation of CAP-based glioblastoma therapy.
