Leukocyte-mimetic liposomes possessing leukocyte membrane proteins pass through inflamed endothelial cell layer by regulating intercellular junctions

• Published in: International journal of pharmaceutics Vol. 563; pp. 314 - 323
• Main Authors: Fukuta, Tatsuya, Yoshimi, Shintaro, Tanaka, Tamotsu, Kogure, Kentaro
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 30.05.2019
• Subjects: Inflamed endothelial cell layer; Inflammatory disease; Intermembrane protein transfer; Leukocyte; Liposome; Vascular endothelial-cadherin; DOPE; Leukocyte; Liposome; ICAM-1; CD11b; Inflammatory disease; CD11a; Inflamed endothelial cell layer; DCP; F-actin; TNF-α; DiIC18; Vascular endothelial-cadherin; VE-cadherin; Intermembrane protein transfer; EPC; HUVEC; HL-60; ATRA; DMPC
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2019.04.027

[Display omitted] 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.