The fast development of photoactivation for cancer treatment provides an efficient photo-therapeutic strategy for cancer treatment, but traditional photodynamic or photothermal therapy suffers from the critical issue of low in vivo penetration depth of tissues. As a non-invasive therapeutic modality, sonodynamic therapy (SDT) can break the depth barrier of photoactivation because ultrasound has an intrinsically high tissue-penetration performance. Micro/nanoparticles can efficiently augment the SDT efficiency based on nanobiotechnology. The state-of-art of the representative achievements on micro/nanoparticle-enhanced SDT is summarized, and specific functions of micro/nanoparticles for SDT are discussed, from the different viewpoints of ultrasound medicine, material science and nanobiotechnology. Emphasis is put on the relationship of structure/composition-SDT performance of micro/nanoparticle-based sonosensitizers. Three types of micro/nanoparticle-augmented SDT are discussed, including organic and inorganic sonosensitizers and micro/nanoparticle-based but sonosensitizer-free strategies to enhance the SDT outcome. SDT-based synergistic cancer therapy augmented by micro/nanoparticles and their biosafety are also included. Some urgent critical issues and potential developments of micro/nanoparticle-augmented SDT for efficient cancer treatment are addressed. It is highly expected that micro/nanoparticle-augmented SDT will be quickly developed as a new and efficient therapeutic modality which will find practical applications in cancer treatment. At the same time, fundamental disciplines regarding materials science, chemistry, medicine and nanotechnology will be advanced.

Micro/Nanoparticle-Augmented Sonodynamic Therapy (SDT): Breaking the Depth Shallow of Photoactivation.

The literature describing the use of low-intensity ultrasound in four major areas of cancer therapy-sonodynamic therapy, ultrasound-mediated chemotherapy, ultrasound-mediated gene delivery and anti-vascular ultrasound therapy-was reviewed. Each technique consistently resulted in the death of cancer cells, and the bio-effects of ultrasound were attributed primarily to thermal actions and inertial cavitation. In each therapeutic modality, theranostic contrast agents composed of microbubbles played a role in both therapy and vascular imaging. The development of these agents is important as it establishes a therapeutic-diagnostic platform that can monitor the success of anti-cancer therapy. Little attention, however, has been given either to the direct assessment of the mechanisms underlying the observed bio-effects or to the viability of these therapies in naturally occurring cancers in larger mammals; if such investigations provided encouraging data, there could be prompt application of a therapy technique in the treatment of cancer patients.

A review of low-intensity ultrasound for cancer therapy.

Peripheral-type" benzodiazepine receptors arelocalized totheouter mitochondrial membrane. Wehave identified potent competitive inhibitors ofthese receptors and purified themfromhumanblood andfromseveral ratorgans. TLC analysis ofthepurified inhibitor fromerythrocytes displays asingle peakofinhibitory activity withanabsorbance spectrum identical tohemin. Alloftheinhibitory activity in extracts ofseveral tissues canbeaccounted forbytheir porphyrin andmetalloporphyrin content. Pureheminand protoporphyrin IXcompetitively inhibit mitochondrial benzo- diazepine binding with K1values of41and15nM,respectively, andareless active byafactor of1000atcentral-type benzo- diazepine receptors. Thus, porphyrins appear tobeendoge- nousligands formitochondrial benzodiazepine receptors. Theanxiolytic effects ofbenzodiazepines aremediated bya "central" benzodiazepine receptor, located primarily inthe brain. However, manybenzodiazepines bindwithhigh af- finity toa"peripheral-type" receptor found innumerous

Porphyrins areendogenous ligands forthemitochondrial (peripheral-type ) benzodiazepine receptor

Recent progress in development of new sonosensitizers for sonodynamic cancer therapy.

Sonodynamic therapy (SDT) has emerged as a promising option for the minimally invasive treatment of solid cancerous tumours. SDT requires the combination of three distinct components: a sensitising drug, ultrasound, and molecular oxygen. Individually, these components are non-toxic but when combined together generate cytotoxic reactive oxygen species (ROS). The major advantage of SDT over its close relative photodynamic therapy (PDT), is the increased penetration of ultrasound through mammalian tissue compared to light. As a result, SDT can be used to treat a wider array of deeper and less accessible tumours than PDT. In this article, we critically review the current literature on SDT and discuss strategies that have been developed in combination with SDT to enhance the therapeutic outcome.

https://www.tandfonline.com/doi/pdf/10.3109/02656736.2014.992484

Treating cancer with sonodynamic therapy: A review

Potential mechanism in sonodynamic therapy and focused ultrasound induced apoptosis in sarcoma 180 cells in vitro.

Membrane fluidity altering and enzyme inactivating in sarcoma 180 cells post the exposure to sonoactivated hematoporphyrin in vitro

In vitro activation of mitochondria-caspase signaling pathway in sonodynamic therapy-induced apoptosis in sarcoma 180 cells.

Damage effects of protoporphyrin IX – Sonodynamic therapy on the cytoskeletal F-actin of Ehrlich ascites carcinoma cells

Sonodynamic therapy (SDT) is a potential cancer therapy based on the synergistic interactions of ultrasound and certain chemical compounds (sono-sensitizers). It has become evident that the direct sonochemical and subsequent redox reactions induced by SDT treatment can lead to apoptotic cell death. However, the detailed mechanisms are not well understood. This study sought to identify the cytotoxic effects of ultrasound-activated protoporphyrin IX (PpIX) on Hepatoma-22 cells (H22). The fluorescence microscope was used to detect the generation of mitochondrial reactive oxygen species (ROS), mitochondrial swelling and release of mitochondrial protein cytochrome c. Several distinct sonochemical effects were found after SDT treatment, including changes of cell viability (decreased to 82.6% in SDT-treated group), generation of mitochondrial ROS, mitochondrial swelling and release of cytochrome c (19.16% in SDT-treated group). These results indicated that the ultrasonically-induced cell killing effect could be enhanced by PpIX, and that the mitochondrial pathway might be involved in the cell damage process.

Wei Tang

Papers

Potential mechanism in sonodynamic therapy and focused ultrasound induced apoptosis in sarcoma 180 cells in vitro.

Membrane fluidity altering and enzyme inactivating in sarcoma 180 cells post the exposure to sonoactivated hematoporphyrin in vitro

In vitro activation of mitochondria-caspase signaling pathway in sonodynamic therapy-induced apoptosis in sarcoma 180 cells.

Damage effects of protoporphyrin IX – Sonodynamic therapy on the cytoskeletal F-actin of Ehrlich ascites carcinoma cells

Induction of sonodynamic effect with protoporphyrin IX on isolate hepatoma-22 cells.