Ultrasmall Barium Titanate Nanoparticles for Highly Efficient Hypoxic Tumor Therapy via Ultrasound Triggered Piezocatalysis and Water Splitting

Abstract

Hypoxia in a solid tumor microenvironment (TME) can lead to the overexpression of hypoxia-inducible factor-1α (HIF-1α), which correlates to tumor metastasis. Reactive oxygen species (ROS) induced tumor cell apoptosis is becoming a promising method in tumor treatment. Currently, the ROS generating systems, e.g., photodynamic treatment and sonodynamic treatment, highly depend on oxygen (O 2 ) in the tumor microenvironment (TME). However, the level of O 2 in TME is too low to produce enough ROS. Herein, we developed an ultrasmall DSPE-PEG 2000 coated barium titanate nanoparticle (P-BTO) for tumor treatment based on ultrasound triggered piezocatalysis and water splitting. Interestingly, irradiated by ultrasound, the surface of ultasmall P-BTO nanoparticles produced imbalance charges, which induced a cascade of redox reaction processes to simultaneously generate ROS and O 2 , the latter one was hardly generated in large-sized barium titanate nanoparticles. The assynthesized P-BTO reached the highest accumulation in the tumor site at 4 h after intravenous injection. The results showed that the produced O 2 significantly alleviated the hypoxia of TME to down-regulate the expression of HIF-1α, and the produced ROS can efficiently kill tumor cells. Moreover, the tumor metastasis was also inhibited, providing a different way to treat triple-negative breast cancer, which was easily metastatic and lacked effective treatments in the clinic.

Near Infrared‐Triggered Theranostic Nanoplatform with Controlled Release of HSP90 Inhibitor for Synergistic Mild Photothermal and Enhanced Nanocatalytic Therapy with Hypoxia Relief

“…Moreover, tumor hypoxia not only causes insufficient therapeutic efficacy but also facilitates tumor angiogenesis, invasion, and metastasis. [ 13 ] To address this issue, enhancing the TME‐responsive supply of oxygen (O 2 ) to tumor sites has been considered as a feasible method for relieving tumor hypoxia. [ 13b ] Fortunately, overexpressed H 2 O 2 in the TME as an entrance can be decomposed into O 2 by catalase (CAT) or CAT‐like nanozyme, for improving the hypoxic TME and augmenting the •OH production.…”

“…[ 13 ] To address this issue, enhancing the TME‐responsive supply of oxygen (O 2 ) to tumor sites has been considered as a feasible method for relieving tumor hypoxia. [ 13b ] Fortunately, overexpressed H 2 O 2 in the TME as an entrance can be decomposed into O 2 by catalase (CAT) or CAT‐like nanozyme, for improving the hypoxic TME and augmenting the •OH production. It has been demonstrated that H 2 O 2 can be catalyzed into highly toxic •OH under acidic conditions, and into O 2 by nanozymes under neutral or weak alkaline conditions.…”

Nanotheranostics for Image-Guided Cancer Treatment

“…C 3 N 4 also serves as PDT agent to synergize with other therapeutic functionalities of the NPs. Similarly, other oxygen-generating photosensitizers have been used to construct NPs with US detectability [ 146 , 147 , 148 ]. For example, Gao et al constructed indocyanine green (ICG) modified hyaluronic acid nanoparticle encapsulating manganese dioxide (MnO 2 ) NPs, which are photosensitizers that react with endogenous H 2 O 2 to generate oxygen bubbles.…”

Fabrication of Injectable Chitosan-Chondroitin Sulfate Hydrogel Embedding Kartogenin-Loaded Microspheres as an Ultrasound-Triggered Drug Delivery System for Cartilage Tissue Engineering

“…The MPs and MPs@KGN dispersion were sonicated for 2 or 5 min using an ultrasound transducer (Chattanooga Co., Chattanooga, TN, USA, Thermal index/Ti = 0.9 and Mechanical index/Mi = 1.6) which had been applied in a previous study [39]. Meanwhile, they were soaked in PBS solution (pH = 7.4) at room temperature for one month.…”