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细胞外囊泡：天然的肝脏蓄积性药物递送载体，用于治疗肝脏疾病。

Extracellular vesicles: Natural liver-accumulating drug delivery vehicles for the treatment of liver diseases.

机构信息

Department of Critical Care Medicine of the Second Affiliated Hospital Zhejiang University School of Medicine Hangzhou China.

Department of Comprehensive Medical Oncology Zhejiang Cancer Hospital Hangzhou China.

出版信息

J Extracell Vesicles. 2020 Dec;10(2):e12030. doi: 10.1002/jev2.12030. Epub 2020 Dec 9.

DOI:10.1002/jev2.12030
PMID:33335695
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7726052/
Abstract

Extracellular vesicles (EVs) are excellent potential vectors for the delivery of therapeutic drugs. However, issues with biological safety and disease targeting substantially limit their clinical application. EVs from red blood cells (RBC-EVs) are potential drug delivery vehicles because of their unique biological safety. Here, we demonstrated that EVs, including RBC-EVs, show natural liver accumulation. Mechanistically, the liver environment induces macrophages to phagocytize RBC-EVs in a C1q-dependent manner. RBC-EVs loaded with antisense oligonucleotides of microRNA-155 showed macrophage-dependent protective effects against acute liver failure (ALF) in a mouse model. These RBC-EVs were also effective in treatment of ALF. Furthermore, compared to routine doses of doxorubicin and sorafenib (SRF), RBC-EVs loaded with doxorubicin or SRF showed enhanced therapeutic effects on a murine model of orthotopic liver cancer through a mechanism dependent on macrophages. Importantly, drug-loaded RBC-EVs showed no systemic toxicity at therapeutically effective doses, whereas routine doses of doxorubicin and SRF showed obvious toxicity. Thus, drug-loaded RBC-EVs hold high potential for clinical applications in the treatment of liver disease therapy.

摘要

细胞外囊泡（EVs）是递送治疗性药物的优秀潜在载体。然而，生物安全性和疾病靶向问题极大地限制了其临床应用。由于具有独特的生物安全性，红细胞来源的 EVs（RBC-EVs）是有潜力的药物递送载体。在这里，我们证明了包括 RBC-EVs 在内的 EVs 具有天然的肝脏蓄积性。在机制上，肝脏环境诱导巨噬细胞以 C1q 依赖性方式吞噬 RBC-EVs。负载 microRNA-155 反义寡核苷酸的 RBC-EVs 在小鼠急性肝衰竭（ALF）模型中显示出巨噬细胞依赖性的保护作用。这些 RBC-EVs 在 ALF 的治疗中也有效。此外，与常规剂量的阿霉素和索拉非尼（SRF）相比，负载阿霉素或 SRF 的 RBC-EVs 通过依赖巨噬细胞的机制，在原位肝癌小鼠模型中显示出增强的治疗效果。重要的是，在治疗有效剂量下，负载药物的 RBC-EVs 没有显示出全身毒性，而常规剂量的阿霉素和 SRF 则显示出明显的毒性。因此，负载药物的 RBC-EVs 在治疗肝脏疾病方面具有很高的临床应用潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc97/7726052/16af9491396e/JEV2-10-e12030-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc97/7726052/6ac36fbc32e8/JEV2-10-e12030-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc97/7726052/fc1c10dc9430/JEV2-10-e12030-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc97/7726052/8f46501240cc/JEV2-10-e12030-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc97/7726052/99b55e6bcb46/JEV2-10-e12030-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc97/7726052/d1e1cb7a67d1/JEV2-10-e12030-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc97/7726052/16af9491396e/JEV2-10-e12030-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc97/7726052/6ac36fbc32e8/JEV2-10-e12030-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc97/7726052/fc1c10dc9430/JEV2-10-e12030-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc97/7726052/8f46501240cc/JEV2-10-e12030-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc97/7726052/99b55e6bcb46/JEV2-10-e12030-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc97/7726052/d1e1cb7a67d1/JEV2-10-e12030-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc97/7726052/16af9491396e/JEV2-10-e12030-g006.jpg

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