Research progress on reactive oxygen species production mechanisms in tumor sonodynamic therapy

Figure 1 Schematic diagram of the different mechanisms of reactive oxygen species generation. A: Schematic diagram of the principle of sonodynamic therapy. Citation: Greenwald BD. Photodynamic therapy for esophageal cancer. Update. Chest Surg Clin N Am 2000; 10(3): 625-637. Copyright © 2011 American Cancer Society, Inc. Published by American Cancer Society, Inc; B: ROS generation by active piezoelectric catalysis. Piezoelectric materials in the electrostatic balance state release charge when under compressive stress and react with H₂O to produce •OH, and O₂ obtains negative charge to generate •O²⁻. Then Piezoelectric materials adsorb the charges from the surrounding electrolyte under reduced compressive stress, H₂O loses negative electrons to generate ·OH, and O₂ releases positive charge to generate •O²⁻. Citation: Wang Y, Wen X, Jia Y, Huang M, Wang F, Zhang X, Bai Y, Yuan G, Wang Y. Piezo-catalysis for nondestructive tooth whitening. Nat Commun 2020; 11(1): 1328. Copyright © The Author(s) 2020. Published by Springer Nature Limited.

Figure 2 Schematic representation of construction of PMR nanosonosensitizers and catalytic oxygen generation-enhanced sonodynamic therapy against cancer. A: Detailed steps for preparation of PMR nanosonosensitizers; B: Scheme of MnOx was used as the catalase-like nanoenzyme for the generation of O₂ and further generation of ¹O₂ under ultrasonic irradiation; C: Confocal laser scanning microscope observation of the production of ROS after various treatment and flow cytometry analysis of cancer cells apoptosis after various treatments; D: Tumor-volume changes after varied treatments; E: Corresponding photographic images of tumor at the end of different treatments. Citation: Zhu P, Chen Y, Shi J. Nanoenzyme-Augmented Cancer Sonodynamic Therapy by Catalytic Tumor Oxygenation. ACS Nano 2018; 12(4): 3780-3795. Copyright © 2018, American Chemical Society. Published by ACS Publication. SDT: Sonodynamic therapy; MnOx: Manganese oxide; H₂O₂: Hydrogen peroxide; US: Ultrasound; ¹O₂: Singlet oxygen; O₂: Oxygen; PpIX: Protoporphyrin; PMR: PpIX@HMONs-MnOx-RGD; PR: Protoporphyrin.

Figure 3 Schematic representation of construction ofα-Fe₂O₃@Pt nanosonosensitizers and catalytic oxygen generation-enhanced SDT against cancer. A, G: Schematic diagram of action mechanism of α-Fe₂O₃@Pt nanoparticles and synthetic method ofα- Fe₂O₃@Pt; B: The relative cell viability of Fe₂O₃ and α- Fe₂O₃@Pt with or without ultrasound under normoxic and hypoxic conditions; C and D: Qualitative and quantitative analysis of ROS by flow cytometer produced by α- Fe₂O₃@Pt; E: Fluorescence image stained with calcein AM (green, live cells) and PI (Propidium iodide, red, dead cells); F: The flow cytometer apoptosis assay staining with PI and Annexin-FTIC; H: Mechanism diagram of O₂ and ROS produced by α- Fe₂O₃@Pt; I: Flow chart of in vivo study experiment; J-M: The variations of d body weight,relative tumor volume, tumor weight and tumor images of mice from different groups after sacrificing the mice on the 14^th day. Citation: Zhang T, Zheng Q, Fu Y, Xie C, Fan G, Wang Y, Wu Y, Cai X, Han G, Li X. α-Fe₂O₃@Pt heterostructure particles to enable sonodynamic therapy with self-supplied O₂ and imaging-guidance. J Nanobiotechnology 2021; 19(1): 358. Copyright © The Author(s) 2021. Published by BioMed Central Ltd. US: Ultrasound; Fe₂O₃: Ferric oxide; Pt: Platinum; FP:α-Fe₂O₃@Pt; ¹O₂: Singlet oxygen; O₂: Oxygen; H₂O₂: Hydrogen peroxide; ROS: Reactive oxygen species.