Biomedical Engineering Reference
In-Depth Information
and longevity are presumed to go hand in hand. A number of approaches
have already been established for the incorporation of targeting ligands
into liposomes so as to maintain this dual functionality [129, 130]. Initially,
ligands were attached directly to the surface of the liposome along with the
PEG lipids. But the steric hindrance of PEG seemed to partially block the
action of the targeting moiety. To overcome this barrier, a majority of the
small molecule ligands are now attached to the distal end of the PEG chain.
3.3.1 Antibody-TargetedLiposomes
It has been repeatedly shown that incorporation of antibodies onto the
surface of liposomes increases their potency by allowing the multivalent
binding to target receptors [131]. Liposomal trastuzumab and rituximab
have been proven to have potent activities both
in vitro
and
in vivo
[132].
Milatuzumab, a CD74 antagonistic monoclonal antibody (mAb), when
incorporated into a liposomal carrier, was shown to be signii cantly more
toxic to chronic lymphocytic leukemia cells [133]. Antibody-targeted
liposomes are frequently used for the site-specii c delivery of hydropho-
bic drugs for the treatment of cancer [134-136]. One of the many advan-
tages of using mAbs is the potential for an additive or synergistic ef ect
between the signaling antibody and the encapsulated drug. Another added
advantage is that specii c antigens expressed in one tumor cell line but not
in others can be targeted [137]. Our group has successfully used cancer-
specii c anti-nucleosome monoclonal antibody 2C5 for tumor delivery of
liposomal doxorubicin [138-140] as well as diagnostic and imaging agents
[141]. More recently, immunoliposomes targeting specii c receptors like
the transferrin receptor [142] and growth factor receptors EGFR [143] and
Her-2 [144] have been developed. h is not only helps the selective deliv-
ery of therapeutic cargo but also serves to competitively block of recep-
tor access to its natural ligands thereby preventing further tumor growth.
Similar preparations have also been successfully used to deliver siRNA to
extra-hepatic targets [145].
Immunoliposomes have also found applications for the treatment of dis-
eases other than cancer. Recently, anti-P-selectin immunoliposomes were
shown to selectively target areas af ected by myocardial infarction [146].
Although antibody-mediated targeting of nanocarriers is generally char-
acterized by high ai nity for the target tissue or organ, continued adminis-
tration can lead to adverse reactions in the body. With this in mind, Cheng
et al.
have used the single chain fragments of the variable region (ScFv)
of the anti-CD19 monoclonal antibody to target liposomal doxorubicin
towards CD19-expressing cells [147]. h ough liposomes with the chain
