A multimodal synergistic anti-glioblastoma strategy based on nano-sonodynamic therapy

Sonodynamic therapy (SDT) has become an effective non-invasive treatment modality. This technique involves the selective activation of sonosensitizers by ultrasound (US) energy, leading to localized production of reactive oxygen species (ROS) and subsequent tumor cell death. Glioblastoma multiforme (GBM) is one of the most prevalent and aggressive primary malignant tumors of the brain, posing a tremendous therapeutic challenge. Although the present treatment is a combination of maximum surgical resection, radiotherapy, and chemotherapy, prognosis is still poor with high recurrence rates. SDT has unique benefits for GBM therapy, specifically the capacity of low-intensity focused US to temporarily and reversibly breach the blood-brain barrier (BBB) to boost the targeted delivery of sonosensitizers and other medication. In addition, US offers high spatial specificity, allowing it to be localized to the tumor and causes minimal destruction to healthy tissue. Nonetheless, SDT has several limitations for clinical translation. These include suboptimal biodistribution and poor tumor-specific targeting of traditional sonosensitizers, attenuation, and distortion of US waves by the skull, and low efficacy in hypoxic tumor regions. The development of nanosonosensitizers is an effective solution to these problems. Designer nanosonosensitizers provide significantly improved targeting, tumor enrichment, and enhanced therapeutic efficacy through more effective optimization of their physicochemical characteristics and incorporation of responsive designs. Herein, the application of SDT in GBM, its limitations and the ways to overcome them, including the combination of SDT and other modalities of treatment, such as chemotherapy, immunotherapy, and targeted gene therapy using nanotechnology, are discussed. With the capability of nanoscience and US technology, these multimodal synergistic strategies hold great potential to enhance the treatment outcomes and the life quality of patients with GBM.