Piezocatalytic Tumor Therapy by Ultrasound‐Triggered and BaTiO₃‐Mediated Piezoelectricity

Abstract

Ultrasound theranostics features non‐invasiveness, minor energy attenuation, and high tissue‐penetrating capability, and is playing ever‐important roles in the diagnosis and therapy of diseases in clinics. Herein, ultrasound is employed as a microscopic pressure resource to generate reactive oxygen species (ROS) for piezocatalytic tumor therapy under catalytic mediation by piezoelectric tetragonal BaTiO3 (T‐BTO). Under the ultrasonic vibration, the electrons and holes are unpaired and they are separated by the piezoelectricity, resulting in the establishment of a strong built‐in electric field, which subsequently catalyzes the generation of ROS such as toxic hydroxyl (•OH) and superoxide radicals (•O2−) in situ for tumor eradication. This modality shows intriguing advantages over typical sonoluminescence‐activated sonodynamic therapy, such as more stable sensitizers and dynamical control of redox reaction outcomes. Furthermore, according to the finite element modeling simulation, the built‐in electric field is capable of modulating the band alignment to make the toxic ROS generation energetically favorable. Both detailed in vitro cellular level evaluation and in vivo tumor xenograft assessment have demonstrated that an injectable T‐BTO‐nanoparticles‐embedded thermosensitive hydrogel will substantially induce ultrasound irradiation‐triggered cytotoxicity and piezocatalytic tumor eradication, accompanied by high therapeutic biosafety in vivo.

Recent Advances in Nanomaterial‐Assisted Combinational Sonodynamic Cancer Therapy

“…using the catalase in RBCs to effectively ameliorate tumor hypoxia and further potentiate the SDT effect. [63] Compared with natural enzymes, nanozymes have been identified as the most promising theranostic adjuvants due to their adjustable enzymatic activity, higher stability, and low production cost. [102] Based on these advantages, An et al developed a biodegradable hollow polydopamine nanoparticle coloaded with the DOX anticancer drug and Ce6 sonosensitizer, further embedded with Pt nanoparticles as catalase-like nanozymes, and modified with TPP mitochondrial-targeting molecules for targeted and catalytic enhanced chemotherapy and SDT to eliminate tumor ( Figure 14A).…”

“…Shi's group recently proposed a piezocatalytic therapy strategy mediated by piezoelectric tetragonal BaTiO 3 nanoparticles (Figure 7F). [ 63 ] Triggered by ultrasonic vibration, the produced electrons and holes were observed to be continuously separated by piezoelectricity, resulting in the formation of a strong built‐in electric field and surface charging, which subsequently catalyzed the generation of ROS for tumor eradication. In addition to the above mentioned, Ag 2 S quantum dots [ 64 ] and copper‐cysteamine [ 65 ] have also been recently found to be sensitized by US.…”

“…Following a similar design, novel Ag 2 S quantum dot nanosonosensitizers were encapsulated into RBC vesicle membranes to prolong the circulation time and catalyze endogenous H 2 O 2 using the catalase in RBCs to effectively ameliorate tumor hypoxia and further potentiate the SDT effect. [ 63 ] Compared with natural enzymes, nanozymes have been identified as the most promising theranostic adjuvants due to their adjustable enzymatic activity, higher stability, and low production cost. [ 102 ] Based on these advantages, An et al.…”

Emerging Nanomedicine‐Enabled/Enhanced Nanodynamic Therapies beyond Traditional Photodynamics

“…By generating microscopic pressure, US was capable of activating noncentrosymmetric tetragonal barium titanate (BaTiO 3 , T‐BTO; Figure 8f) as the piezoelectric material for ROS production including hydroxyl and superoxide radicals. [ 102 ] Similar to BP nanosheets, the piezoelectricity of T‐BTO induced the electrons and holes separation for establishing the strong built‐in electric field. It subsequently triggered ROS production (Figure 8g).…”

p-n Heterojunction-based Thermoelectric Generator for Highly Efficient Cancer Thermoelectric Therapy

“…[34][35][36][37][38][39][40] Further analysis of the mechanism of TE materials shows the separated electron-hole pairs under build-in thermoelectric eld demonstrating great potentials in catalyzing reactive oxygen species (ROS) generation in cushy conditions, similar with the mechanisms of photodynamic therapy and piezocatalytic therapy. 41,42 In addition, compared with PTTgenerated hyperthermia, the ROSs have much shorter lifetime and propagation distance in vivo, presumably guaranteeing much less treatment-related side effect or toxicity on surrounding normal tissues and organs. Although TE generators have grown into superstars in the application elds of energy and environment, it is still an infant in biomedical elds.…”