Citation: Zehua Hong, Xin Zan, Ting Yu, Yuzhu Hu, Hongfeng Gou, Songping Zheng, Xiang Gao, Peizhi Zhou. Local delivery of superagonist gene based on polymer nanoparticles for cancer immunotherapy[J]. Chinese Chemical Letters, ;2023, 34(3): 107603. doi: 10.1016/j.cclet.2022.06.026 shu

Local delivery of superagonist gene based on polymer nanoparticles for cancer immunotherapy

Department of Neurosurgery and Institute of Neurosurgery, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China

zhengsongping2022@163.com

peizhizhouns@126.com

Received Date: 13 March 2022
Revised Date: 8 June 2022
Accepted Date: 9 June 2022
Available Online: 14 June 2022

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Cancer is the leading cause that threatens human life expectancy due to the lack of effective therapies. Cancer immunotherapy has been explored to improve the body's immune system against cancer and accompanied by promising results in recent years. Interleukin 15 (IL-15), a pleiotropic immunomodulator, is critical for immune cells development and displays great anti-tumor potential in both preclinical and clinical trials. In this study, superagonist IL-15 plasmid (psIL-15) consisting of IL-15Rα-sushi-linker-IL-15 was constructed in order to secret superagonist IL-15 (sIL-15) in tumor site. A gene delivery system through self-assembly by methylated polyethylene glycol-b-polylactic acid-b-methylated polyethylene glycol (mPEG-PLA-mPEG) and 1, 2-dioleoyl-3-trimethylammonium-propane (DOTAP), named DMAM, was designed to deliver psIL-15. Further study showed that DMAM/psIL-15 could successfully deliver psIL-15 to tumor cells and the supernatants of the tumor cells could further stimulate lymphocytes proliferation as well as activation in vitro. Local delivery of DMAM/psIL-15 in animal models demonstrated significant tumor inhibition through enhancing immune cells responses, reducing angiogenesis, promoting tumor cell apoptosis and inhibiting proliferation, with no evidence of system toxicities. These results indicate that DMAM/psIL-15 may be a promising strategy for cancer immunotherapy.
- IL-15,
- Immunotherapy,
- Gene therapy,
- Nanoparticles,
- Tumor
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沈阳化工大学材料科学与工程学院沈阳 110142