Postdoctoral Researcher n/a Sydney, New South Wales, Australia
Abstract: Glioblastoma (GBM) is a highly aggressive and common brain tumor with resistance to conventional therapies, leading to poor outcomes and a median survival of less than 15 months. The ability to resist apoptotic signals, evade the immune system, and high recurrence and adaptability of GBM cells further underscore the urgent need for transformative therapeutic strategies. To tackle these challenges, we propose a novel polytherapy combining delivery of optimal low-intensity ultrasound (LIUS) with piezoelectric nanoparticles (PNPs) for direct electrotoxicity and enhancing chemotherapy efficacy. PNPs generate localized electric fields upon ultrasound activation, amplifying reactive oxygen species (ROS) production in cells, oxidative stress, and apoptosis, as wells as altering cytoskeletal dynamics, compromising GBM cell structure and motility. Our work demonstrates pre-clinical proof-of-concept for nano-electro-chemotherapy, including unique direct electrotoxicity and affirming augmented chemotherapy of GBM. The approach synergizes mechanical, chemical, and electrical stimuli to also overcomes resistance mechanisms inherent to GBM. Notwithstanding the potential for treating other solid tumors, this innovative polytherapy represents a promising step toward developing more effective, targeted, and less invasive treatments for GBM. By integrating advanced nanotechnology with ultrasound-based delivery systems, we provide a foundation for further preclinical and clinical investigations with the aim of improving cancer patient outcomes.
Funding Source: Funding to support the research for this manuscript was provided by the Arto Hardy Family, Tour de Cure, and Tregaskis Foundation.
