Theranostics
2022; 12(17):7465-7475.
doi:10.7150/thno.75007 This issueCite
Research Paper
Self-immolative nanosensitizer for glutathione depletion- assisted sonodynamic therapy
Chan Ho Kim1*, Dong Gil You1*, Pramod Kumar E. K.1, Kyung Hee Han1, Wooram Um1, Jeongjin Lee2, Jae Ah Lee1, Jae Min Jung1, Heegun Kang1, Jae Hyung Park1,2,3✉
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.
✉ Corresponding author: Jae Hyung Park, School of Chemical Engineering, Sungkyunkwan University, 2066 Seobu-ro, Jangan-gu, Suwon 16419, Republic of Korea. E-mail: jhpark1edu.
Citation:
Kim CH, You DG, E. K. PK, Han KH, Um W, Lee J, Lee JA, Jung JM, Kang H, Park JH. Self-immolative nanosensitizer for glutathione depletion- assisted sonodynamic therapy. Theranostics 2022; 12(17):7465-7475. doi:10.7150/thno.75007. https://www.thno.org/v12p7465.htm
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.
Kim, C.H., You, D.G., E. K., P.K., Han, K.H., Um, W., Lee, J., Lee, J.A., Jung, J.M., Kang, H., Park, J.H. (2022). Self-immolative nanosensitizer for glutathione depletion- assisted sonodynamic therapy. Theranostics, 12(17), 7465-7475. https://doi.org/10.7150/thno.75007.
ACS
Kim, C.H.; You, D.G.; E. K., P.K.; Han, K.H.; Um, W.; Lee, J.; Lee, J.A.; Jung, J.M.; Kang, H.; Park, J.H. Self-immolative nanosensitizer for glutathione depletion- assisted sonodynamic therapy. Theranostics 2022, 12 (17), 7465-7475. DOI: 10.7150/thno.75007.
NLM
Kim CH, You DG, E. K. PK, Han KH, Um W, Lee J, Lee JA, Jung JM, Kang H, Park JH. Self-immolative nanosensitizer for glutathione depletion- assisted sonodynamic therapy. Theranostics 2022; 12(17):7465-7475. doi:10.7150/thno.75007. https://www.thno.org/v12p7465.htm
CSE
Kim CH, You DG, E. K. PK, Han KH, Um W, Lee J, Lee JA, Jung JM, Kang H, Park JH. 2022. Self-immolative nanosensitizer for glutathione depletion- assisted sonodynamic therapy. Theranostics. 12(17):7465-7475.
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