Abstract
Reversible thiol-disulfide exchange chemistry is of particular interest in drug delivery systems. However, high levels of glutathione (GSH) in cancer cells are hard to distinguish from GSH in normal cells, resulting in unmanageable cytotoxic drug release. This study investigates the spatiotemporally-controlled irreversible degradation of Ir-based photosensitizer (TIr3)-encapsulating nanogels (IrNG) through the hyperoxidation of resulting intracellular thiols using reactive oxygen species (ROS). A highly cytotoxic TIr3 was stably encapsulated within IrNG through hydrophobic interactions and reversible crosslinking between its disulfide bonds and thiols in the absence of light, resulting in high biocompatibility under normal cellular conditions. However, upon photoirradiation, TIr3 generated high levels of ROS, irreversibly oxidizing the thiols to induce electrostatic repulsion between the polymer molecules, resulting in the TIr3 release and induction of cancer cell apoptosis.
| Original language | English |
|---|---|
| Article number | e202210623 |
| Journal | Angewandte Chemie - International Edition |
| Volume | 61 |
| Issue number | 42 |
| DOIs | |
| Publication status | Published - 2022 Oct 17 |
Bibliographical note
Funding Information:We thank Yoon Ji Choi, Yoon Hee Kwon, and Soo Ah Park from the Ulsan National Institute of Science & Technology (UNIST) in vivo Research Center (IVRC) for in vivo technical support, including H&E staining and tumor modelling. We thank Hee Sik Son, Hyun Kyeong Seo and Jeong Hwan Lim from the UNIST Central Research Facilities (UCRF) for obtaining the ICP-OES, LC-MS/MS, and TEM data, respectively. We also thank Chang-Mo Yoo (Seoul National University) for providing the plasmids (BFP-Sec61B). This work was supported by the Ulsan National Institute of Science & Technology (UNIST) (Research Fund 1.220026.01), the National Research Foundation of Korea (NRF) (Grant numbers 2017M3A7B4052802, 2021M3H4A1A03051390, 2021R1A2C2009504, 2018R1A5A1025208, and 2021R1A2C3004978), National Cancer Center (NCC) (Research Fund HA22C010100), Korea Technology & Information Promotion Agency for SMEs (TIPA) (grant S3198656) and INNOPOLIS Foundation (2021-IT-RD-0338). C.G.L. acknowledges support from the Global Ph.D. Fellowship Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF-2018H1A2A1061237).
Funding Information:
We thank Yoon Ji Choi, Yoon Hee Kwon, and Soo Ah Park from the Ulsan National Institute of Science & Technology (UNIST) in vivo Research Center (IVRC) for in vivo technical support, including H&E staining and tumor modelling. We thank Hee Sik Son, Hyun Kyeong Seo and Jeong Hwan Lim from the UNIST Central Research Facilities (UCRF) for obtaining the ICP‐OES, LC‐MS/MS, and TEM data, respectively. We also thank Chang‐Mo Yoo (Seoul National University) for providing the plasmids (BFP‐Sec61B). This work was supported by the Ulsan National Institute of Science & Technology (UNIST) (Research Fund 1.220026.01), the National Research Foundation of Korea (NRF) (Grant numbers 2017M3A7B4052802, 2021M3H4A1A03051390, 2021R1A2C2009504, 2018R1A5A1025208, and 2021R1A2C3004978), National Cancer Center (NCC) (Research Fund HA22C010100), Korea Technology & Information Promotion Agency for SMEs (TIPA) (grant S3198656) and INNOPOLIS Foundation (2021‐IT‐RD‐0338). C.G.L. acknowledges support from the Global Ph.D. Fellowship Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF‐2018H1A2A1061237).
Publisher Copyright:
© 2022 Wiley-VCH GmbH.
All Science Journal Classification (ASJC) codes
- Catalysis
- Chemistry(all)
