Exosome-Modified Tissue Engineered Blood Vessel for Endothelial Progenitor Cell Capture and Targeted siRNA Delivery.

Abstract

Instability and poor targeting causes the long-term patency of RNA-modified tissue engineering blood vessels (TEBVs) remaining unsatisfactory. RNA can be enriched in exosome and then delivered into targeted cells while whether exosome-modified TEBVs achieve RNA targeted delivery is unclear. Here, to promote the expression of klotho protein on the mesenchymal stem cell (MSC)-derived exosomes, klotho plasmids are first transfected into MSCs, and adenosine kinase (ADK) siRNA is then loaded into exosome (klotho/ADK siRNA-exosome) using electrotransfection. Flow chamber results show that klotho/ADK siRNA-exosome can effectively capture circulating endothelial progenitor cells (EPCs). Besides, the captured EPCs can endocytose this exosome, and then decompose it into klotho protein and ADK siRNA. Moreover, ADK siRNA promotes the paracrine of proangiogenic factors and adenosine from EPCs, which further facilitate proliferation and migration of endothelial cells. Based on polyethyleneimine-capped gold nanoparticles, exosome-modified TEBVs are constructed through layer-by-layer assembly. Animal experimental results show that klotho/ADK siRNA-exosome-modified TEBVs can maintain the patency up to one month, and good endothelialization is observed. In short, one exosome-modified TEBV is constructed, capture molecules on the surface of exosome capture the circulating EPCs, and the loaded RNA achieves its purpose of accurate treatment depending on the needs of patients.