Complement Activation, Immunogenicity, and Immune Suppression as Potential Side Eff ects of Liposomes - Harnessing Biomaterials in Nanomedicine: Preparation, Toxicity, and Applications - page 313

adverse immune responses to liposomes. It was our goal to highlight
the common grounds of immune stimulation, to provide examples
of reactogenicity, immunogenicity and immune suppression, and to
outline recent theories about the mechanism of these phenomena.

11.3 General Causes Behind Immune

Recognition of Liposomes

Among many structural features, two stand out as fundamental
reasons for immune recognition of liposomes: (1) the diameter of
vesicles, roughly in the 50-200 nm range and (2) absence on the
liposomal bilayer surface of those membrane proteins or other
structures that are present on blood cells and endothelial cells,
which normally prevent these cells from C attack. As for the size
factor, Table 11.2 shows that there is a remarkable overlap between
the size range of many clinically used liposomes and pathogenic
human viruses belonging to diff erent viral families. This overlap,
however, may not be simple coincidence, but rather the consequence
of those common physicochemical rules and forces that force bilayer
membranes to form vesicles in live systems and in test tubes; in
fact, liposomes are considered as the archetype bilayer vesicles that
predated cellular evolution over millions of years [9, 23, 24].
As a remarkable example of common natural forces involved in
the formation of viruses and liposomes, Figure 11.2 shows that the
visual appearance of Doxil (a) is almost indistinguishable from that
of HIV-1 (b). Figure 11.2c also illustrates that most globular viruses
under the electron microscope look very much like large unilamellar
vesicles (LUV), while paramyxoviruses look like typical multilamellar
vesicles (MLV). Of note, hepatitis B surface antigen particles are
almost indistinguishable from small unilammelar vesicles (SUV)
[26].
In addition to viruses, liposomes also resemble ectosomes,
i.e., membrane vesicles detached from cells, as well as most
other ecto-organelles and cellular debris that form upon cell
death. Nanobacteria, the smallest self-replicating pathogens, are
also in the liposome size range (100-200 nm) [19]. In essence,
liposomes mimic the size and shape of pathogenic microbes and
some subcellular structures against which nature developed
strong eliminatory mechanisms via humoral and cellular immune
responses.