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Theranostics 2022; 12(17):7465-7475. doi:10.7150/thno.75007 This issue Cite
Research Paper
1. School of Chemical Engineering, College of Engineering, Sungkyunkwan University, 2066 Seobu-ro, Jangan-gu, Suwon 16419, Republic of Korea.
2. Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, 81 Irwon-ro, Gangnam-gu, Seoul, 06351 Republic of Korea.
3. Biomedical Institute for Convergence at SKKU (BICS), Sungkyunkwan University, 2066 Seobu-ro, Jangan-gu, Suwon 16419, Republic of Korea.
*These authors contributed equally to this work.
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 GSHhigh cancer cells into GSHlow 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.
Keywords: self-immolative polymer, TiO2 nanoparticles, reactive oxygen species, glutathione, sonodynamic therapy