Biomedical Engineering Reference
In-Depth Information
DNA, attack cells of the cardiovascular system, leading to the decay
of the blood vessels in critical organs such as the kidneys. In this
way, SLE is a classic demonstration of the dangerous inflammation
mediated by autoantibodies. Plasmid DNA has routinely been
administered to both animals and humans in gene therapy and
gene vaccination trials apparently without significant induction of
allergic responses. An often-cited report by Madaio [55] also found
that the injection of DNA seemed to induce no significant antibody
response. However, an important point also made in this report was
the observation that the structure of the DNA molecules aff ected the
immunogenicity such that poly(dG):poly(dC), poly(dT-dG):poly(dC-
dA), and left-handed Z-DNA were more able than B-DNA to induce
an immune response [55]. This clearly raises a question concerning
the consequences of administering a large amount of DNA with a
complex structure to the body.
An important source of biopolymers used in nanotechnology
is constituted by charged lipids applied for the formation of lipid
vesicles or liposomes. Through relatively simple procedures such as
the extrusion of lipid suspensions, it is possible to create liposomes
with well-defined sizes and the ability to perform targeted transport
of drugs, typically by conjugating the liposomes with antibodies to
cell surface markers on target cells [56]. In the case of cancer therapy,
liposomes have also been conjugated with RGD peptides to facilitate
the uptake by
β
1
and
β
3
integrin-expressing cells. Many animal
models have shown the efficacy of such strategies with regard to the
suppression of inflammation and slowing of cancer cell growth [57].
A less studied area is leukocyte activation by artificial liposomes. Both
microbial organisms and the immune cells produce a large number
of vesicular structures. In the case of bacteria, these structures may
well contribute to immune evasion by acting as a decoy target for
antibodies or other proteins binding to microbial surface structures
[58]. Leukocytes liberate a large number of vesicles in the process of
migration in the tissue [59]. The homeostasis of lipids is maintained
by number of specialized receptors expressed on many cell types,
including macrophages, which ingest lipid particles in blood. The
uptake by leukocytes is interesting as lipids play a major role in
leukocyte signaling and resolution of inflammation [60]. Therefore, it
is not surprising that reports have found several immunomodulatory
eff ects of the administration of lipids. Also, it is well established that
the inclusion of, in particular, cationic lipids may serve as an adjuvant
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