Archaeosomes prepared from aeropyrum pernix K1 lipids as an in vivo targeted delivery system for subsequent nanosecond electroporation

Abstract

The search for an ideal delivery system capable of targeted delivery of therapeutic molecules to tumor cells after a systemic administration is ongoing. Recently liposomes prepared from archaeal lipids (archaeosomes) emerged as a viable alternative to traditional liposomes. They are highly stable and have low toxicity in vitro. But even once inside the cell, they still do not release their cargo. Thus, when combined with nanosecond electroporation nsEP, which permeabilizes small vesicles inside the cell, presents an attractive delivery system with spatial and temporal control of the therapeutic molecules delivery. Therefore, the aim of our study was to determine the in vivo stability of archaeosomes from Aeropyrum pernix K1 and their extravasation from tumor blood vessels. We used intravital video microscopy to determine the circulation time of archaeosomes in normal and tumor blood vessels and whether they extravasate from tumor blood vessels. Additionally, their stability after exposure to mouse blood in situ was determined. The intravenously injected archaeosomes were circulating for 6 minutes in normal and tumor blood vessels and showed a preference for increased retention in tumor blood vessels. The measured size of archaeosomes in vivo varied from 200 nm up to several thousand nm, due to aggregation of archaeosomes when in contact with blood, which was confirmed in situ. The obtained results elucidate the behavior of archaeosomes from A. pernix in vivo and indicate future steps necessary to make them a viable delivery system potentially combined with nsEP.