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Theranostics 2022; 12(17):7465-7475. doi:10.7150/thno.75007 This issue Cite

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
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Abstract

Graphic 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 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

Citation styles

APA
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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