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Review
. 2022 Jun 9;9(1):26.
doi: 10.1186/s40779-022-00386-z.

Nanosensitizers for sonodynamic therapy for glioblastoma multiforme: current progress and future perspectives

Qing-Long Guo #  1   2 , Xing-Liang Dai #  2 , Meng-Yuan Yin  1   2 , Hong-Wei Cheng  3 , Hai-Sheng Qian  1 , Hua Wang  4 , Dao-Ming Zhu  5 , Xian-Wen Wang  6
Affiliations
Review

Nanosensitizers for sonodynamic therapy for glioblastoma multiforme: current progress and future perspectives

Qing-Long Guo et al. Mil Med Res. .

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.

Keywords: Blood–brain barrier (BBB); Combination therapy; Glioblastoma multiforme (GBM); Sonodynamic therapy (SDT); Sonosensitizers.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Fig. 1
Fig. 1
Schematic of SDT strategies for the treatment of GBM. GBM glioblastoma multiforme, PDT photodynamic therapy, ROS reactive oxygen species, SDT sonodynamic therapy, US ultrasound, MRI magnetic resonance imaging
Fig. 2
Fig. 2
Standard treatment strategy for GBM. GBM glioblastoma multiforme, RT radiotherapy, TMZ temozolomide, TTF tumor treating fields, MGMT O6-methylguanine-DNA methyltransferase, HFRT hyperfractionated radiotherapy, KPS Karnofsky performance score, BSC best supportive care, PCV procarbazine, lomustine, and vincristine regimen, NCCN National Comprehensive Cancer Network
Fig. 3
Fig. 3
Physiological and pathophysiological structures of the blood–brain barrier (BBB). BBB structure alterations in brain tumors and types of small molecules that cross the BBB. a Tight junction in physiological status, < 1 nm. b Tight conjunction in tumor bearing status, > 7 nm. c Approximately 20 nm
Fig. 4
Fig. 4
Schematic overview of the SDT mechanisms in gliomas. a General SDT mechanism. b US activation of the sonosensitizers accumulate in the mitochondria could induce the generation of ROS, which would result in the mitochondria swelling and mitochondria membrane potential (MMP) decreasing. Meanwhile, the degradation of the sarcoplasmic/endoplasmic reticulum Ca2+ ATPase (SERCA2) can lead to an abnormal increase in calcium. Both mechanisms can eventually promote apoptosis of glioma cells. SDT sonodynamic therapy, US ultrasound, ROS reactive oxygen species
See this image and copyright information in PMC

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