Yoshimi, Shintaro Tokushima University
Intermembrane protein transfer
Inflamed endothelial cell layer
Nanoparticles such as liposomes have been applied for the treatment of various diseases such as cancer and inflammatory diseases by utilizing the enhanced permeability and retention effect. However, their entry into inflammation sites is still limited since passive delivery of nanoparticles is often hampered by the presence of endothelial barriers. As leukocytes can pass through the inflamed endothelium via utilizing membrane protein functions, we hypothesized that incorporating leukocyte membrane proteins onto liposomal membranes may impart leukocyte-mimicking functions to liposomes, allowing for their adherence to and active passage through the inflamed endothelium. Herein, we developed leukocyte-mimetic liposomes (LM-Lipo) by leukocyte membrane protein transfer and evaluated their function in vitro. Transfer of membrane proteins from human leukemia cells onto liposomal membranes allowed for significant association of the liposomes with inflamed human endothelial cells, and subsequent passage through inflamed endothelial cell layer. The confocal images showed that LM-Lipo significantly induced vascular endothelial-cadherin displacement. These results indicate that LM-Lipo adhered to and regulated intercellular junctions of inflamed endothelial cell layer, resulting in passage through the layer, by mimicking the function of leukocytes. Furthermore, it is suggested that liposomes possessing leukocyte-like functions could be useful for drug delivery to inflammation sites by overcoming endothelial barriers.
International Journal of Pharmaceutics
© 2019. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/
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