Liposomes (alias smectic mesophases of membrane phospholipids) were presented as valid models of biological cell membranes by my laboratory some 40 years ago. They became iconic structures for delivery of toxic drugs such as the polyene antibiotics, cisplatin and doxorubicin (see review by Vladimir Torchilin Nature Reviews Drug Delivery  4:145-160). Google suggests that as many as 500,000 patents have been processed since our initial publication (AD Bangham, MMStandish and JC Watkins, J.Mol. Biol (1965). 238-252).
Like most alien particles introduced into the circulation of animals, liposomes were instantly recognised as being foreign and removed by the reticuloendothelial system. Anonymity is difficult to sustain if one enters the blood stream, or for that matter, the tissues of an animal. Almost all surfaces are tagged within milliseconds of being exposed to plasma, which after all is an abundant source of animal glue! Both the tagging and the gluing are spontaneous events and a result of the release of electrostatically bound water as the ionic groups of surface and protein mutually satisfy their respective charge. The driving force for the spontaneity of the adsorption/gluing process is, in addition to various attractive forces, the disordering of bound water. But suppose the surface of the material introduced into the plasma already looks like the surface of a slice of (bulk) water; the polyionic proteins will not then find anything to tag, there is no entropy gain, no attractive interactions and the interloper is invisible.
‘Stealth’ liposomes were developed by a company (Liposome Technology) started by a career scientist who worked in my department and was largely responsible for promoting liposome technology in the US. Knowing that proteins did not adhere to starch (biochemists were using starch beds for the electrophoresis of proteins) Liposome Technology was able, by attaching polyethylene oxide onto liposomes, to generate particles that survived for long periods in patients, thus the name ‘Stealth’. The Stealth story has suggested to me that mismatched organ transplants might also be protected if the raw surface (presenting unprotected MHCs (major histocompatibility complex) are shielded by a bouquet of volatile aminoacids. The latter suggestion has been made by me for the surprising reason that mice can identify their siblings by smelling their urine. Human pheronomes have recently been shown to be unique to an individual thus suggesting that they may be profiling a person’s MHC.
Alec Bangham formerly worked at the ARC Institute of Animal Physiology, Babraham. His personal website can be read here.