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Reactive Oxygen Species‐Responsive Protein Modification and Its Intracellular Delivery for Targeted Cancer Therapy
Abstract
Herein we report a convenient chemical approach to reversibly modulate protein (RNase A) function and develop a protein that is responsive to reactive oxygen species (ROS) for targeted cancer therapy. The conjugation of RNase A with 4‐nitrophenyl 4‐(4,4,5,5‐tetramethyl‐1,3,2‐dioxaborolan‐2‐yl) benzyl carbonate (NBC) blocks protein lysine and temporarily deactivates the protein. However, the treatment of RNase A–NBC with hydrogen peroxide (one major intracellular ROS) efficiently cleaves the NBC conjugation and restores the RNase A activity. Thus, RNase A–NBC can be reactivated inside tumor cells by high levels of intracellular ROS, thereby restoring the cytotoxicity of RNase A for cancer therapy. Due to higher ROS levels inside tumor cells compared to healthy cells, and the resulting different levels of RNase A–NBC reactivation, RNase A–NBC shows a significant specific cytotoxicity against tumor cells.
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Cited by
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Xu, X., Saw, P. E., Tao, W., Li, Y., Ji, X., Bhasin, S., Liu, Y., Ayyash, D., Rasmussen, J., Huo, M., et al. (2017) · Advanced Materials · doi:10.1002/adma.201700141 · Cited by 499
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Metadata
- Authors
- Wang, M., Sun, S., Neufeld, C. I., Perez‐Ramirez, B., & Xu, Q.
- Venue
- Angewandte Chemie International Edition
- Publisher
- Wiley
- Published
- 2014-10-06
- Volume
- 53
- Issue
- 49
- Pages
- 13444-13448
- ISSN
- 1433-7851 (ISSN-L)
- 1521-3773
- OpenAlex
- W2117969524
- Cited by
- 249
- References
- 0
- FWCI
- 6.08
- Type
- journal article
- Language
- en
- Open access
- closed
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- Wang, M., Sun, S., Neufeld, C. I., Perez‐Ramirez, B., & Xu, Q. (2014). Reactive Oxygen Species‐Responsive Protein Modification and Its Intracellular Delivery for Targeted Cancer Therapy. Angewandte Chemie International Edition. https://doi.org/10.1002/anie.201407234
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