Long-circulating, polyethylene glycol-grafted immunoliposomes

In the last few years a number of advances took place in development of methodologies for preparation of polyethylene glycol (PEG)-grafted immunoliposomes. Several new end-group functionalized PEG lipids were introduced for this purpose. These include pyridyldithiopropionate-PEG- and hydrazide-PEG-PE derivatives, which incorporate well into liposomes and are used for covalent attachment of antibodies to extremities of the liposome-grafted polymeric chains. Methods previously known for linking antibodies to classical liposomes are in some cases applicable to preparation of PEG-grafted immunoliposomes. In these methods antibodies are fixed directly to the lipid bilayer through reactive residues on the polar headgroups of lipids. Attributes of the new methods and their comparison to the traditional methods for preparation of immunoliposomes are the main focus of this manuscript. Particular attention is paid to reactivities, potential and observed complications as well as to the relationship between the conjugation chemistry and biological activity. It is clear that having numerous possible pathways for generating long-circulating immunoliposomes is of great value, since some antibodies tend to be sensitive to different chemical conditions. The current state of the field should facilitate rapid accumulation of in vivo results, which are critical for determination of the true value of this technology.