Glioblastoma (GBM), the most lethal primary brain tumor in adults, is characterized by extensive infiltration, marked heterogeneity, and resistance to conventional therapies. The blood-brain barrier (BBB) impedes effective drug delivery; therefore, recent advancements in energy-based therapies have introduced innovative approaches to overcome these challenges. These include focused ultrasound, tumor-treating fields, magnetomechanical actuation, and triboelectric stimulation to transiently disrupt the BBB and facilitate targeted treatment. Piezodynamic therapy has emerged as a key strategy, using piezoelectric nanomaterials to convert mechanical stimuli into reactive oxygen species (ROS) and immunogenic signals, inducing localized oxidative stress and immune activation. This approach is complemented by nanogas-based technologies, which enhance spatiotemporal control over ROS generation through ultrasound-driven piezocatalysis. Novel 3D-bioprinted GBM models provide patient-specific platforms for optimizing these therapies and investigating piezodynamic effects in realistic tumor environments. Concurrently, implantable smart devices enable real-time modulation of mechanical stimuli, improving treatment precision. Tumor vaccines also play a complementary role by amplifying systemic anti-GBM immune responses. Challenges such as nanoparticle biocompatibility, precise regulation of physical stimuli, and clinical translation persist. This review evaluates the existing energy-based multimodal treatments and integration of piezodynamic therapy with nanogas technologies, 3D bioprinting, and immune-stimulating vaccines, highlighting their potential as a featuristic strategy to overcome GBM's therapeutic resistance.
Muhammad et al. (2025) studied this question.