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Abstract Glioblastoma multiforme (GBM) is the most common primary malignant brain tumor, and it is associated with poor prognosis. Its characteristics of being highly invasive and undergoing heterogeneous genetic mutation, as well as the presence of the blood–brain barrier (BBB), have reduced the efficacy of GBM treatment. The emergence of a novel therapeutic method, namely, sonodynamic therapy (SDT), provides a promising strategy for eradicating tumors via activated sonosensitizers coupled with low-intensity ultrasound. SDT can provide tumor killing effects for deep-seated tumors, such as brain tumors. However, conventional sonosensitizers cannot effectively reach the tumor region and kill additional tumor cells, especially brain tumor cells. Efforts should be made to develop a method to help therapeutic agents pass through the BBB and accumulate in brain tumors. With the development of novel multifunctional nanosensitizers and newly emerging combination strategies, the killing ability and selectivity of SDT have greatly improved and are accompanied with fewer side effects. In this review, we systematically summarize the findings of previous studies on SDT for GBM, with a focus on recent developments and promising directions for future research.

Interleukin 17 (IL-17) and its main producer, T cell receptor γδ cells, have neurotoxic effects in the pathogenesis of intracerebral hemorrhage (ICH), aggravating brain injuries. To investigate the correlation between IL-17 and ICH, we dynamically screened serum IL-17 concentrations using enzyme-linked immunosorbent assay and explored the clinical values of IL-17 in ICH patients. There was a significant negative correlation between serum IL-17 level and neurological recovery status in ICH patients (r = –0.498, P < 0.01). To study the neurotoxic role of IL-17, C57BL/6 mice were used to establish an ICH model by injecting autologous blood into the caudate nucleus. Subsequently, the mice were treated with mouse neural stem cells (NSCs) and/or IL-17 neutralizing antibody for 72 hours. Flow cytometry, brain water content detection, Nissl staining, and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling results indicated that NSC transplantation significantly reduced IL-17 expression in peri-hematoma tissue, but there was no difference in T cell receptor γδ cells. Compared with the ICH group, there were fewer apoptotic bodies and more Nissl bodies in the ICH + NSC group and the ICH + NSC + IL-17 group. To investigate the potential effect of IL-17 on directional differentiation of NSCs, we cultured mouse NSCs (NE-4C) alone or co-cultured them with T cell receptor γδ cells, which were isolated from mouse peripheral blood mononuclear cells, for 7 days. The results of western blot assays revealed that IL-17 secreted by T cell receptor γδ cells reduced the differentiation of NSCs into astrocytes and neurons, while IL-17 neutralization relieved the inhibition of directional differentiation into astrocytes rather than neurons. In conclusion, serum IL-17 levels were elevated in the early stage of ICH and were negatively correlated with outcome in ICH patients. Animal experiments and cytological investigations therefore demonstrated that IL-17 probably has neurotoxic roles in ICH because of its inhibitory effects on the directional differentiation of NSCs. The application of IL-17 neutralizing antibody may promote the directional differentiation of NSCs into astrocytes. This study was approved by the Clinical Research Ethics Committee of Anhui Medical University of China (For human study: Approval No. 20170135) in December 2016. All animal handling and experimentation were reviewed and approved by the Institutional Animal Care and Use Committee of Anhui Medical University (approval No. 20180248) in December 2017.