2. Academic Validation
  3. Reprogramming Exosomes to Escape from Immune Surveillance for Mitochondrial Protection in Hepatic Ischemia-Reperfusion Injury

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

  • Theranostics. 2024 Jan 1;14(1):116-132. doi: 10.7150/thno.88061.
Shanshan Liu 1 2,  Xinyu Xiao 1,  La Zhang 3,  Jianwei Wang 1,  Wei Zhao 1,  Haichuan Liu 3,  Rui Liao 3,  Zhi Li 4,  Mengxia Xu 4,  Jiao Guo 1,  Baoyong Zhou 3,  Chengyou Du 3,  Qiling Peng 1 5,  Ning Jiang 6 7 8
Affiliations

Affiliations

  • 1 School of Basic Medical Science, Chongqing Medical University, Chongqing 400016, P. R. China.
  • 2 Department of Plastic and Maxillofacial Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P. R. China.
  • 3 Department of Hepatobiliary Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P. R. China.
  • 4 Traditional Chinese Medicine Hospital of Bijie City, Guizhou province, 551700, People's Republic of China.
  • 5 Bijie Municipal Health Bureau, Guizhou province, 551700, People's Republic of China.
  • 6 Department of Pathology, Chongqing Medical University, Chongqing 400016, P. R. China.
  • 7 Molecular Medicine Diagnostic and Testing Center, Chongqing Medical University, Chongqing 400016, P. R. China.
  • 8 Department of Pathology, the First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P. R. China.
PMID: 38164154 DOI: 10.7150/thno.88061
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

CD47; Cyclosporin A; Exosomes; Hepatic ischemia/reperfusion injury; Macrophages; Mitochondria.

Figures
Products