Full Text | PDF

Share on tweeters Share on facebook Share on linkedin Share on googleplus

Theranostics 2024; 14(1):116-132. doi:10.7150/thno.88061 This issue Cite

Research Paper

Reprogramming Exosomes to Escape from Immune Surveillance for Mitochondrial Protection in Hepatic Ischemia-Reperfusion Injury

Shanshan Liu1,8†, Xinyu Xiao1†, La Zhang2†, Jianwei Wang1†, Wei Zhao1, Haichuan Liu2, Rui Liao2, Zhi Li3, Mengxia Xu3, Jiao Guo1, Baoyong Zhou2✉, Chengyou Du2✉, Qiling Peng1,4✉, Ning Jiang5,6,7✉

1. School of Basic Medical Science, Chongqing Medical University, Chongqing 400016, P. R. China.
2. Department of Hepatobiliary Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P. R. China.
3. Traditional Chinese Medicine Hospital of Bijie City, Guizhou province, 551700, People's Republic of China.
4. Bijie Municipal Health Bureau, Guizhou province, 551700, People's Republic of China.
5. Department of Pathology, Chongqing Medical University, Chongqing 400016, P. R. China.
6. Molecular Medicine Diagnostic and Testing Center, Chongqing Medical University, Chongqing 400016, P. R. China.
7. Department of Pathology, the First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P. R. China.
8. Department of Plastic and Maxillofacial Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P. R. China.
† These authors contributed equally to this work.

✉ Corresponding authors: E-mail: sdlytczhzhcom (Baoyong Zhou); duchengyoucom (Chengyou Du); pqlpzyedu.cn (Qiling Peng); jiangningedu.cn (Ning Jiang)

Citation:
Liu S, Xiao X, Zhang L, Wang J, Zhao W, Liu H, Liao R, Li Z, Xu M, Guo J, Zhou B, Du C, Peng Q, Jiang N. Reprogramming Exosomes to Escape from Immune Surveillance for Mitochondrial Protection in Hepatic Ischemia-Reperfusion Injury. Theranostics 2024; 14(1):116-132. doi:10.7150/thno.88061. https://www.thno.org/v14p0116.htm
Other styles

File import instruction

Abstract

Graphic abstract

Background: Therapeutic interventions such as synthetic drugs and microRNA (miR) modulators have created opportunities for mitigating hepatic ischemia/reperfusion injury (HIRI) by alleviating mitochondrial dysfunction. However, delivering multi-therapeutic ingredients with low toxicity to hepatocytes still lags behind its development.

Methods: In this study, we endowed exosomes with delivery function to concentrate on hepatocytes for multidimensionally halting mitochondria dysfunction during HIRI. Concretely, exosomes were reprogrammed with a transmembrane protein CD47, which acted as a “camouflage cloak” to mimic the “don't eat me” mechanism to escape from immune surveillance. Besides, HuR was engineered bridging to the membrane by fusing with CD47 and located in the cytoplasm for miR loading.

Results: This strategy successfully delivered dual payloads to hepatocytes and efficiently protected mitochondria by inhibiting the opening of mitochondrial permeability transition pore (mPTP) and upregulating mitochondrial transcription factor A (TFAM), respectively.

Conclusions: The reprogramming of exosomes with CD47 and HuR for targeted delivery of CsA and miR inhibitors represents a promising therapeutic strategy for addressing HIRI. This approach shows potential for safe and effective clinical applications in the treatment of HIRI.

Keywords: Exosomes, Hepatic ischemia/reperfusion injury, Macrophages, CD47, Mitochondria, Cyclosporin A

Citation styles

APA
Liu, S., Xiao, X., Zhang, L., Wang, J., Zhao, W., Liu, H., Liao, R., Li, Z., Xu, M., Guo, J., Zhou, B., Du, C., Peng, Q., Jiang, N. (2024). Reprogramming Exosomes to Escape from Immune Surveillance for Mitochondrial Protection in Hepatic Ischemia-Reperfusion Injury. Theranostics, 14(1), 116-132. https://doi.org/10.7150/thno.88061.

ACS
Liu, S.; Xiao, X.; Zhang, L.; Wang, J.; Zhao, W.; Liu, H.; Liao, R.; Li, Z.; Xu, M.; Guo, J.; Zhou, B.; Du, C.; Peng, Q.; Jiang, N. Reprogramming Exosomes to Escape from Immune Surveillance for Mitochondrial Protection in Hepatic Ischemia-Reperfusion Injury. Theranostics 2024, 14 (1), 116-132. DOI: 10.7150/thno.88061.

NLM
Liu S, Xiao X, Zhang L, Wang J, Zhao W, Liu H, Liao R, Li Z, Xu M, Guo J, Zhou B, Du C, Peng Q, Jiang N. Reprogramming Exosomes to Escape from Immune Surveillance for Mitochondrial Protection in Hepatic Ischemia-Reperfusion Injury. Theranostics 2024; 14(1):116-132. doi:10.7150/thno.88061. https://www.thno.org/v14p0116.htm

CSE
Liu S, Xiao X, Zhang L, Wang J, Zhao W, Liu H, Liao R, Li Z, Xu M, Guo J, Zhou B, Du C, Peng Q, Jiang N. 2024. Reprogramming Exosomes to Escape from Immune Surveillance for Mitochondrial Protection in Hepatic Ischemia-Reperfusion Injury. Theranostics. 14(1):116-132.

This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
Popup Image

©2024 Ivyspring International Publisher. Terms of use