Biomedical Engineering Reference
In-Depth Information
the endosome at a lower pH releasing the encapsulated contents in the
cytoplasm in the vicinity of the nucleus [240]. Recently, targeted liposo-
mal formulations were complexed with polyethylenimine (PEI) for the
ei cient delivery of DNA [241, 242] and siRNA [243]. Similarly, lipo-
somes containing dendrimer-DNA complexes have also been developed
[244]. Octaarginine-targeted fusogenic liposomes loaded with bleomy-
cin demonstrated strong anti-tumor activity in a murine 4T1 tumor
model [245]. Similarly, liposomes targeted with peptides that released
their contents in a pH -sensitive [246] as well as temperature-sensitve
manner were developed [247]. Antibodies have also successfully been
used with triggered release systems [248]. pH-sensitive doxorubicin
liposomes with anti-HER2 antibodies [249] as well as anti-EGFR gem-
citabine liposomes [250] have been developed. Taking multi-functional
approaches a step further, dual ligand-targeted liposomes with stimuli-
sensitive functions have been suggested. Recently, Koren
et al.
showed
the ei ciency of doxorubicin liposomes targeted with 2C5 antibody and
TATp (see Figure 3.3) [251]. h e targeted liposome was coated with
PEG-hydrazone-PE which dissociates at a lower pH, typical of tumor
Fibroblasts
MCF-7
B16-F10
(
a
)
(
b
)
(
c
)
(
d
)
(
e
)
Figure 3.3
Fluorescence microscopy showing the internalization of rhodamine-PE-
labeled liposomes. (a) Plain liposomes (b) TATp-modii ed liposomes (c)2C5-modii ed
liposomes (d)TATp-2C5-hydrazone-modii ed liposomes pre-incubated at pH 7.4 and
(e) TATp-2C5-hydrazone-modii ed liposomes pre-incubated at pH 5 are shown.
(Red-rhodamine; Blue-hoechst nuclei staining) From [251] Reproduced with the
permission of Elsevier.
