Oxygen‐Independent Synchronized ROS Generation and Hypoxia Prodrug Activation with Z‐Scheme Heterostructure Sonosensitizer

Abstract

Combination therapy has emerged as a promising approach for effective tumor treatment. However, the combination of sonodynamic therapy (SDT) and hypoxia‐activated prodrugs (HAPs) has not been explored due to the contradictory requirement of oxygen (O2) for reactive oxygen species (ROS) generation and the necessity to avoid O2 for the activation of HAPs. In this study, we address this challenge by developing BiOCl‐Au‐Ag2S Z‐scheme heterostructure nanoparticles loaded with tirapazamine (TPZ) to achieve O2‐independent therapy. These nanoparticles demonstrate efficient electron‐hole separation under ultrasound irradiation while maintaining a high redox potential. The generated holes react with water to efficiently produce hydroxyl radicals, while the electrons autonomously activate TPZ, negating the need for O2. In vitro and in vivo assessments validate the effective tumor elimination by these Z‐scheme nanoparticles without disrupting the hypoxic environment. This innovative design overcomes the limitations associated with O2 requirement in SDT and introduces a novel strategy for HAP activation and synergistic therapy between ROS and HAP‐based therapy.This article is protected by copyright. All rights reserved

Ultrasound-Controlled Prodrug Activation: Emerging Strategies in Polymer Mechanochemistry and Sonodynamic Therapy

“…•− radical Recently, Cheng, Chen and co-workers developed BiOCl− Au-Ag2S Z-scheme heterostructure nanoparticles loaded with a redox-activatable drug tirapazamine (TPZ). 136 These nanoparticles showed efficient electron−hole separation under ultrasound irradiation and exhibited a high redox potential. The resulting redox environment activated the redoxresponsive drug TPZ, which exhibited cytotoxicity to tumor both in vitro and in vivo.…”

“…Recently, Cheng, Chen and co-workers developed BiOCl–Au-Ag2S Z-scheme heterostructure nanoparticles loaded with a redox-activatable drug tirapazamine (TPZ) . These nanoparticles showed efficient electron–hole separation under ultrasound irradiation and exhibited a high redox potential.…”

Ultrasound-Based Micro-/Nanosystems for Biomedical Applications

“…Notably, noncovalent π–π stacking is also instrumental in drug loading for delivery systems − and in the self-assembly of micro-/nanoscale systems . Anticancer compounds, sonosensitizers, and biomacromolecules , have been effectively encapsulated into delivery systems through π–π interactions. This interaction has also been harnessed for the self-assembly of novel delivery systems using diverse materials like graphene-based materials, carbon-based substances, micelles, and hydrogels .…”