Research progress of tumor sonodynamic therapy based on nanomaterials

Abstract

<p indent=0mm>Sonodynamic therapy (SDT) is a new technique for tumor therapy developed on the basis of photodynamic therapy (PDT). Compared with PDT, SDT has many advantages, such as non-invasive, deep tissue penetration, safety, among others. The enhanced antitumor efficacy of SDT is mainly originated from the ultrasound activation of sonosensitizers accumulated at the tumor site. However, the exact mechanism of SDT is still under study. Low frequency ultrasound, molecular oxygen and sonosensitizers are the key factors of SDT, especially the sonosensitizers, which are most closely related to the SDT efficacy. At present, most of the sonosensitizers derive from photosensitizers, such as porphyrins and their derivatives. These traditional sonosensitizers are usually poor in water solubility, blood circulation and tumor targeting, leading to the unsatisfactory tumor site enrichment and SDT efficacy. The novel nanomaterials-based sonosensitizers can effectively overcome the above-mentioned disadvantages and promote SDT application. Owing to the large specific surface area, high loading capacity and ease to combine with biomarkers, nanomaterials have been applied in SDT as carriers to improve the bioavailability of traditional sonosensitizers and enhance the SDT efficacy. In addition, some new types of inorganic sonosensitizers based on sonosensitive inorganic nanomaterials exhibited better physical and chemical properties and stability in SDT application than organic sonosensitizers. Moreover, nanomaterials can be endowed with new characteristics by surface modification by taking advantage of their unique physical and chemical properties, such as the surface, structure and size. For example, modification of nano-sonosensitizers with oxygen supply or tumor targeting ability can alleviate the hypoxic treatment environment of SDT and increase the accumulation of sonosensitizers at tumor site. In addition, nanomaterials-based sonosensitizers provide SDT with more possibilities when combined with chemotherapy, photothermal therapy, photodynamic therapy, and immunotherapy, among others, playing significant roles in improving the anti-tumor therapeutic effect. This review begins with the summarization of the therapeutic mechanisms of SDT, including ultrasonic cavitation effect, reactive oxygen species effect, and tumor microenvironment regulation effect, among others. Next, we mainly introduce the progress of nanomaterials-based sonosensitizers for cancer SDT in recent years, including the application of polymers, liposomes, and inorganic nanomaterials as traditional sonosensitizer carriers for the enhancement of SDT efficacy, as well as metal, silicon, and carbon-based nanomaterials with sound sensitive effect for the development of SDT-based new therapeutic strategies. Finally, we summarize the aspects of the future development of SDT. Despite many advantages, there are still some issues worth to be considered for nanomaterials-based tumor SDT in the future. On the one hand, mechanisms of SDT for tumor therapy are still not clear and remain controversial, and further elucidation are still required for effective and precise treatment for different tumor models. On the other hand, it is still full of challenges to develop novel sonosensitizer with low toxicity and high efficacy. Therefore, to shed light on SDT mechanisms and explore innovative and efficient sonosensitizers will be the key to the future development of SDT.