Biomedical Engineering Reference
In-Depth Information
3.3.2.3
Targeting with Sugar Moieties
An interesting concept in the targeting of liposomes has been the use of
sugar moieties [171]. Recently, the targeting potential of mannose-coated
liposomes was demonstrated [172] and subsequently mannose- and lac-
tose-coated liposomes have been successfully used for the cellular delivery
of genes [173] and antigens [174]. Sialylneolacto-N-tetraose c (LSTc)-
bearing liposomes were used to bind to inl uenza A virus thereby inhibit-
ing infection [175]. Fucosylated liposomes were shown to ef ectively target
Kupf er cells to deliver NF-kB decoys [176]. Another interesting approach
has been the use of lectins like Sialyl Lewis X as targeting moieties [177].
h ese lectins target E-selectins, which are generally overexpressed during
inl ammation[178].
3.3.2.4
Peptides as Targeting Moieties
Peptide-targeted liposomes have many advantages and have been widely
used for the delivery of chemo-therapeutic drugs [179], DNA[180] and
siRNA [181, 182]. h ey are smaller and more labile than antibodies and
can be easily chemically synthesized depending on the target-selectivity.
In recent years, advances in the i eld have led to a development of phage-
coat peptide libraries for the ei cient targeting of nanocarriers [183]. h ese
can be specii cally engineered [184] to bind to specii c cell surface recep-
tors [185] and proteins [186] with high ai nity. A few studies have been
carried out in order to optimize the development of these phage-directed
nanocarriers [187]. Use of these peptide ampiphiles allows for a more sta-
ble liposomal structure [188], which results in prolonged in vivo stability.
Peptide-targeted liposomes have been proposed as delivery vehicles for
boron neutron capture therapy [189] as well as for the targeting of brain
endothelium [190] and lung tumor models in vivo [191]. Recently, the
targeting of angiogenic chaperone proteins like BiP/GRP78 using specii c
peptides have been shown to be an ef ective strategy to suppress tumor
growth [192]. In an interesting study by Rivera-Fillat et al. , the antian-
giogenic ef ects of the liposomal doxorubicin targeted by thrombospon-
din peptidomimetics was demonstrated [193]. h e targeted formulation
reduced tumor growth by almost 60% in a murine HT29 tumor model.
Another interesting strategy has been to target growth factor receptors
on tumors with peptides [194]. Similarly, truncated human basic i bro-
blast growth factor peptide was used to target liposomal doxorubicin and
paclitaxel to prostate and melanoma tumors, respectively, in mice [195].
Falciani et al. have very elegantly demonstrated the use of a branched
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