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      Nanoparticle-assisted ultrasound: A special focus on sonodynamic therapy against cancer

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          Abstract

          At present, ultrasound radiation is broadly employed in medicine for both diagnostic and therapeutic purposes at various frequencies and intensities. In this review article, we focus on therapeutically-active nanoparticles (NPs) when stimulated by ultrasound. We first introduce the different ultrasound-based therapies with special attention to the techniques involved in the oncological field, then we summarize the different NPs used, ranging from soft materials, like liposomes or micro/nano-bubbles, to metal and metal oxide NPs. We therefore focus on the sonodynamic therapy and on the possible working mechanisms under debate of NPs-assisted sonodynamic treatments. We support the idea that various, complex and synergistics physical–chemical processes take place during acoustic cavitation and NP activation. Different mechanisms are therefore responsible for the final cancer cell death and strongly depends not only on the type and structure of NPs or nanocarriers, but also on the way they interact with the ultrasonic pressure waves. We conclude with a brief overview of the clinical applications of the various ultrasound therapies and the related use of NPs-assisted ultrasound in clinics, showing that this very innovative and promising approach is however still at its infancy in the clinical cancer treatment.

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          Mechanisms of nanotoxicity: Generation of reactive oxygen species⋆

          Nanotechnology is a rapidly developing field in the 21 st century, and the commercial use of nanomaterials for novel applications is increasing exponentially. To date, the scientific basis for the cytotoxicity and genotoxicity of most manufactured nanomaterials are not understood. The mechanisms underlying the toxicity of nanomaterials have recently been studied intensively. An important mechanism of nanotoxicity is the generation of reactive oxygen species (ROS). Overproduction of ROS can induce oxidative stress, resulting in cells failing to maintain normal physiological redox-regulated functions. This in turn leads to DNA damage, unregulated cell signaling, change in cell motility, cytotoxicity, apoptosis, and cancer initiation. There are critical determinants that can affect the generation of ROS. These critical determinants, discussed briefly here, include: size, shape, particle surface, surface positive charges, surface-containing groups, particle dissolution, metal ion release from nanometals and nanometal oxides, UV light activation, aggregation, mode of interaction with cells, inflammation, and pH of the medium.
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            Micro/Nanoparticle-Augmented Sonodynamic Therapy (SDT): Breaking the Depth Shallow of Photoactivation.

            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.
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              Molecular events associated with reactive oxygen species and cell cycle progression in mammalian cells.

              Cell cycle progression is regulated by a wide variety of external factors, amongst them are growth factors and extracellular matrix factors. During the last decades evidence has been obtained that reactive oxygen species (ROS) may also play an important role in cell cycle progression. ROS may be generated by external and internal factors. In this overview we describe briefly the generation of ROS and their effects on processes that have been demonstrated to play an essential role in cell cycle progression, including such systems as signal transduction cascades, protein ubiquitination and degradation, and the cytoskeleton. These different effects of ROS influence cell cycle progression dependent upon the amount and duration of ROS exposure. Activation of growth factor stimulated signaling cascades by low levels of ROS result in increased cell cycle progression, or, in case of prolonged exposure, to a differentiation like growth arrest. From many studies it seems clear that the cyclin kinase inhibitor protein p21 plays a prominent role, leading to cell cycle arrest at higher but not directly lethal levels of ROS. Dependent upon the nature of p21 induction, the cell cycle arrest may be transient, coupled to repair processes, or permanent. At high concentrations of ROS all of the above processes are activated, in combination with enhanced damage to the building blocks of the cell, leading to apoptosis or even necrosis.
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                Author and article information

                Journal
                9892118
                34265
                Chem Eng J
                Chem Eng J
                Chemical engineering journal (Lausanne, Switzerland : 1996)
                1385-8947
                12 March 2019
                15 May 2018
                15 March 2019
                : 340
                : 155-172
                Affiliations
                [a ]Department of Applied Science and Technology, Politecnico di Torino, Corso Duca degli Abruzzi 24, 10129 Turin, Italy
                [b ]Center for Sustainable Future Technologies CSFT@Polito, Istituto Italiano di Tecnologia, Corso Trento 21, 10129, Turin, Italy
                Author notes
                [* ]Corresponding author at: Department of Applied Science and Technology, Politecnico di Torino, Corso Duca degli Abruzzi 24, 10129 Turin, Italy. valentina.cauda@ 123456polito.it (V. Cauda).
                Article
                EMS82206
                10.1016/j.cej.2018.01.060
                6420022
                30881202
                7fc778dc-41be-48b4-b488-a26a629757e5

                This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/BY-NC-ND/4.0/).

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                Categories
                Article

                inertial cavitation,reactive oxygen species,sonoluminescence,sonodynamic,tumor therapy,cytotoxicity

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