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Sonodynamic therapy (SDT) is a promising non-invasive therapeutic modality. Compared to photo-inspired therapy, SDT provides many opportunities and benefits, including deeper tissue penetration, high precision, less side effects, and good patient compliance. Thanks to the facile engineerable nature of nanotechnology, nanoparticles-based sonosensitizers exhibit predominant advantages, such as increased SDT efficacy, binding avidity, and targeting specificity. This review aims to summarize the possible mechanisms of SDT, which can be expected to provide the theoretical basis for SDT development in the future. We also extensively discuss nanoparticle-assisted sonosensitizers to enhance the outcome of SDT. Additionally, we focus on the potential strategy of combinational SDT with other therapeutic modalities and discuss the limitations and challenges of SDT toward clinical applications.

Sonodynamic therapy (SDT), as a novel non-invasive strategy for eliminating tumor, has the advantages of deeper tissue penetration, fewer side effects, and better patient compliance, compared with photodynamic therapy (PDT). In SDT, ultrasound was used to activate sonosensitizer to produce cytotoxic reactive oxygen species (ROS), induce the collapse of vacuoles in solution, and bring about irreversible damage to cancer cells. In recent years, much effort has been devoted to developing highly efficient sonosensitizers which can efficiently generate ROS. However, the traditional organic sonosensitizers, such as porphyrins, hypericin, and curcumins, suffer from complex synthesis, poor water solubility, and low tumor targeting efficacy which limit the benefits of SDT. In contrast, inorganic sonosensitizers show good in vivo stability, controllable physicochemical properties, ease of achieving multifunctionality, and high tumor targeting, which greatly expanded their application in SDT. In this review, we systematically summarize the nanomaterials which act as the carrier of molecular sonosensitizers, and directly produce ROS under ultrasound. Moreover, the prospects of inorganic nanomaterials for SDT application are also discussed.

With the development of engineered nanomaterials and nanomedicines, utilization of nanomaterials to generate excessive reactive oxygen species under exogenous ultrasound (US) irradiation for realizing disease therapy, namely sonodynamic therapy (SDT), has attracted widespread attention. Compared with traditional photodynamic therapy, US shows deeper tissue penetration to reach deep‐seated location. However, the development of high‐efficiency sonosensitizers remains one of the gravest challenges in current related research and future clinical application. Latterly, benefiting from the piezotronic and piezo‐phototronic effects, novel sonosensitizers based on piezoelectric semiconductor (PS) nanomaterials have exhibited inspiring application prospects in SDT. In this review, we outline the structures and physicochemical properties of PS nanomaterials that has potential applications in SDT, and introduce the presumed mechanisms of PS nanomaterials in SDT. Then, the latest research progress of PS nanomaterials as sonosensitizers in cancer therapy and antibacterial applications are summarized. Finally, the existing challenges and future development trends in this field are prospected. Benefiting from the piezotronic and piezo‐phototronic effect, sonosensitizers based on piezoelectric semiconductor (PS) nanomaterials have shown promising application prospects in sonodynamic therapy. In this review, the latest research progress of PS nanomaterials as sonosensitizers in cancer therapy and antibacterial applications are summarized.

Sonodynamic therapy (SDT) is an emerging non-invasive cancer treatment method in the field of nanomedicine, which has the advantages of deep penetration, good therapeutic efficacy, and minimal damage to normal tissues. Sonosensitizers play a crucial role in the process of SDT, as their structure and properties directly determine the treatment outcome. Inorganic sonosensitizers, with their high stability and longer circulation time in the human body, have great potential in SDT. In this review, the possible mechanisms of SDT including the ultrasonic cavitation, reactive oxygen species generation, and activation of immunity are briefly discussed. Then, the latest research progress on inorganic sonosensitizers is systematically summarized. Subsequently, strategies for optimizing treatment efficacy are introduced, including combination therapy and image-guided therapy. The challenges and future prospects of sonodynamic therapy are discussed. It is hoped that this review will provide some guidance for the screening of inorganic sonosensitizers.

Immunogenic cell death (ICD) has been demonstrated as a reliable approach to improve therapeutic effect in cancer treatment by triggering antitumor immunity. However, the trigger of ICD on the basis of chemotherapy and phototherapy meets the obstacles of serious side effect and poor penetration ability, which seriously impedes the therapeutic effect. The development of sonodynamic immunotherapy with the evoking of ICD presents high promise for cancer treatment with high efficacy. Herein, high performance aggregation‐induced emission (AIE) sonosensitizer is constructed on the basis of the engineering structure modulation for sonodynamic‐augmented immunotherapy. By regulating the intermolecular interaction and pull‐push electronic effect, sonosensitizer bearing AIE feature and amplified sono‐sensitizing effect is developed. In addition, in vitro observation demonstrated that thiolate‐substituted segment incorporation endows the molecules with enhanced cellular uptake efficiency and improved tumor cell eradication ability. More importantly, the developed sonosensitizer could efficiently evoke ICD upon the trigger of ultrasound, which allows for the efficient tumor eradication both at cellular level and in solid tumor. The inhibition of primary tumor and further boost systemic immunity response with the complete elimination toward the distant tumor is achieved. The investigation highlights the promise of utilizing AIE sonosensitizers in sonodynamic immunotherapy to conquer the current limitation of immunotherapy in solid tumor treatment. The development of sonodynamic immunotherapy with the evoking of immunogenic cell death presents high promise for cancer treatment in biosafe and penetrated manner. Based on engineering structure modulation by regulating intermolecular interaction and push‐pull electronic effect, high performance aggregation‐induced emission (AIE) sonosensitizer with accelerated cellular uptake ability and improved ROS generation effect is constructed for sonodynamic‐augmented immunotherapy, allowing for complete elimination of both primary and distant tumor.

As a non-invasive strategy, sonodynamic therapy (SDT) which utilizes sonosensitizers to generate reactive oxygen species (ROS) has received significant interest over recent years due to its ability to break depth barrier. However, intrinsic limitations of traditional sonosensitizers hinder the widespread application of SDT. With the development of nanotechnology, various nanoparticles (NPs) have been designed and used to assist sonosensitizers for SDT. This review first summarizes the possible mechanisms of SDT, then classifies the NPs-assisted sonosensitizers and discusses their biomedical applications in ultrasonography, drug delivery, high intensity focused ultrasound and SDT-based combination treatment. Finally, some challenges and future perspectives of NPs-assisted SDT has also been discussed.

With the rapid development of sonodynamic therapy (SDT), sonosensitizers have evolved from traditional treatments to comprehensive diagnostics and therapies. Sonosensitizers play a crucial role in the integration of ultrasound imaging (USI), X-ray computed tomography (CT), and magnetic resonance imaging (MRI) diagnostics while also playing a therapeutic role. This review was based on recent articles on multifunctional sonosensitizers that were used in SDT for the treatment of cancer and have the potential for clinical USI, CT, and MRI applications. Next, some of the shortcomings of the clinical examination and the results of sonosensitizers in animal imaging were described. Finally, this paper attempted to inform the future development of sonosensitizers in the field of integrative diagnostics and therapeutics and to point out current problems and prospects for their application.

Sonodynamic therapy (SDT) typically suffers from compromised anticancer efficacy owing to the low reactive oxygen species (ROS) yield and complicated tumor microenvironment (TME) which can consume ROS and support the occurrence and development of tumors. Herein, ultrathin‐FeOOH‐coated MnO2 nanospheres (denoted as MO@FHO) as sonosensitizers which can not only facilitate ultrasound (US)‐triggered ROS but also tune the TME by hypoxia alleviation, H2O2 consumption as well as glutathione (GSH) depletion are designed. The FeOOH coating will boost the production yield of singlet oxygen (1O2) and hydroxyl radicals (•OH) by inhibiting the recombination of US‐initiated electron–hole pairs and Fenton‐like reaction, respectively. Additionally, the catalase‐like and GSH peroxidase‐like activities of MO@FHO nanospheres enable them to break the TME equilibrium via hypoxia alleviation and GSH depletion. The combination of high ROS yield and fundamental destruction of TME equilibrium results in satisfactory antitumor outcomes, as demonstrated by the high tumor suppression efficacy of MO@FHO on MDA‐MB‐231‐tumor‐bearing mice. No obvious toxicity is detected to normal tissues at therapeutic doses in vivo. The capability to modulate the ROS production and TME simultaneously can afford new probability for the development of advanced sonosensitizers for synergistic comprehensive cancer therapy. A MnO2@FeOOH sonosensitizer is constructed to achieve oncotherapy by modulating reactive oxygen species (ROS) yield and tumor microenvironment. FeOOH coverage acts as hole conductor and O2 production cocatalyst to improve ROS production and alleviate hypoxia. The H2O2 and glutathione depletions are detected by its Fenton‐like and glutathione peroxidase‐like activities. The antitumor efficacy is testified both in vitro and in vivo.

Sonodynamic therapy is a potential cancer treatment modality that has been gaining support due to its effectiveness in both in vitro and in vivo studies. The therapeutic method combines ultrasonic irradiation with drugs known as sonosensitizers that amplify its ability to inflict preferential damage on malignant cells. This is based on the idea that ultrasonic waves have the ability to exhibit profound physical and chemical changes on cellular structure. The mechanisms by which ultrasound (US) disrupts cellular functioning can be further amplified when sonosensitizers are applied. Combining multiple sonosensitizers with US to create a substantial synergistic effect could be an effective method for destroying tumorigenic growths, while decreasing the likelihood of drug resistance.

Sonodynamic therapy （SDT） is an emerging approach that involves a combination of low-intensity ultrasound and specialized chemical agents known as sonosensitizers. Ultrasound can penetrate deeply into tissues and can be focused into a small region of a tumor to activate a sonosensitizer which offers the possibility of non-invasively eradicating solid tumors in a site-directed manner. In this article, we critically reviewed the currently accepted mechanisms of sonodynamic action and summarized the classification of sonosensitizers. At the same time, the breath of evidence from SDT-based studies suggests that SDT is promising for cancer treatment.