Abstract
Despite the biomedical advances of the last century, many cancers including glioblastoma are still resistant to existing therapies leaving patients with poor prognoses. Nanosecond pulsed electric fields (nsPEF) are a promising technology for the treatment of cancer that have thus far been evaluated in vitro and in superficial malignancies. In this paper, we develop a tumor organoid model of glioblastoma and apply intravital multiphoton microscopy to assess their response to nsPEFs. We demonstrate for the first time that a single 10 ns, high voltage electric pulse (35–45 kV/cm), collapses the perfusion of neovasculature, and also alters the diameter of capillaries and larger vessels in normal tissue. These results contribute to the fundamental understanding of nsPEF effects in complex tissue environments, and confirm the potential of nsPEFs to disrupt the microenvironment of solid tumors such as glioblastoma.
Highlights
Despite the biomedical advances of the last century, many cancers including glioblastoma are still resistant to existing therapies leaving patients with poor prognoses
Cultured glioblastoma cells (U87-MG) stably expressing green fluorescent protein (GFP) were grafted into developing quail eggs in a developmental window (8.5 embryonic day) when the chorioallantoic membrane (CAM) exhibited a vasoproliferative response that facilitated the growth of the tumor (Fig. 1a)[20]
The method permitted the growth of fluorescent, spheroidal, millimeter size, vascularized tumors that could be treated with Nanosecond pulsed electric fields (nsPEF) during intravital multiphoton microscopy sessions (Fig. 2a,b)
Summary
Despite the biomedical advances of the last century, many cancers including glioblastoma are still resistant to existing therapies leaving patients with poor prognoses. We develop a tumor organoid model of glioblastoma and apply intravital multiphoton microscopy to assess their response to nsPEFs. We demonstrate for the first time that a single 10 ns, high voltage electric pulse (35–45 kV/cm), collapses the perfusion of neovasculature, and alters the diameter of capillaries and larger vessels in normal tissue. The brain cancer glioblastoma multiforme (GBM) is incurable and leaves patients with an average survival of approximately 14.6 months after initial diagnosis, despite multimodal treatment with surgery, radiotherapy and chemotherapy[1] Emerging bioelectric therapies such as electrochemotherapy, electrogenetherapy[2,3] and irreversible electroporation[4] have yet to be applied clinically on human cancers of the brain, but preclinical studies have shown the potential of these electroporation-based technologies in neuro-oncology[5,6]. The influence of nsPEFs on tumor vasculature was investigated using multiphoton intravital imaging to demonstrate that a single nsPEF pulse was www.nature.com/scientificreports/
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