ABSTRACT
Background: Despite remarkable advances in sonodynamic therapy (SDT) of cancer, the low reactive oxygen species (ROS) quantum yield of the sonosensitizer remains a critical concern in glutathione (GSH)-overexpressing cancer cells. Methods: For enhanced SDT, we report hydrophilized self-immolative polymer (SIP)-decorated TiO2 nanoparticles (HSIPT-NPs) to achieve on-demand GSH depletion and ROS generation. Results: Upon intracellular delivery of HSIPT-NPs into hydrogen peroxide-rich cancer cells, SIP is degraded through electron transfer to produce GSH-depleting quinone methide, reprogramming GSH high cancer cells into GSH low phenotype. In the presence of ultrasound, compared to conventional TiO2 NPs, HSIPT-NPs induce significantly higher oxidative stress to cancer cells by incapacitating their antioxidant effects. SDT with HSIPT-NPs effectively inhibit tumor growth in mice via the synergistic effects of GSH depletion and ROS generation. Conclusion: On the basis of their ability to reprogram cancer cells, HSIPT-NPs offer considerable potential as a nanosensitizer for enhanced SDT.
Subject(s)
Nanoparticles , Neoplasms , Mice , Animals , Reactive Oxygen Species/metabolism , Glutathione/metabolism , Antioxidants/pharmacologyABSTRACT
With interest in non-invasiveness and safety in cancer treatment, sonodynamic therapy (SDT) has emerged as a promising alternative to conventional cancer therapies. SDT offers safety and cost-effectiveness and exhibits a broad application range that is superior to photodynamic therapy. However, the insufficient reactive oxygen species (ROS) production of current sonosensitizers has hindered its clinical application to date. In this review, the ROS-generation mechanism in SDT and the limitations of current sonosensitizers are briefly reviewed. Also, highlighted are recent nanomaterial-based SDT strategies to improve the efficiency of sonosensitizers, amplify oxidative stress, and elicit antitumor immunity.
