Recent Advances with Liposomes as Drug Carriers - Advanced Biomaterials and Biodevices - page 94

liposomes were developed as an angiogenesis targeting agent for imaging
applications [217].
Another interesting approach was the use of an adenovirus as a target-
ing moiety to deliver genetic cargo to cancer cells [218].
3.3.3 Dual-TargetedLiposomes
To take the targeting strategies of nanoparticulates one step further,
a new approach to targeted drug delivery has emerged in the last i ve
years. Dual-targeting employs the use of two dif erent targeting ligands
attached to the surface of the same carrier. Many target cell types like
tumor cells express many dif erent types of receptors and/or antigens
on their surface. h e attachment of more than one ligand onto the lipo-
some allows for a higher target binding ei ciency thus increasing the
accumulation of liposomal cargo [219]. One of the main focuses of this
dual targeting strategy has been in anticancer therapy [220-223]. Chen
et al. have used liposomes targeted with RGD and octeotride to selec-
tively target cancers of the GI tract with greater ei ciency than mono-
ligand-modii ed liposomes [224]. In another study, liposomes with
hepatocyte targeting and nuclear targeting capabilities were used for the
ei cient delivery of DNA [225]. In a recent study by Gao et al. , doxoru-
bicin liposomes targeted with Tf and folic acid were developed with the
assumption that Tf would help facilitate penetration across the BBB and
the folate would allow for ef ective internalization into the tumor vascu-
lature [226]. Similarly, daunorubicin-loaded liposomes targeted with Tf
and p-aminophenyl-α-D-manno-pyranoside were also developed [227].
In vivo , the dual targeted liposomes were able to increase the survival
time and reduce tumor volume when compared to the single ligand
formulations. h e benei ts of dual targeting were also demonstrated by
Jiang et al. who developed paclitaxel-loaded liposomes targeted with
hyaluronic acid (HA) and an arginine-rich cell-penetrating peptide in
the hope that in the tumor microenvironment, when the HA is hydro-
lyzed by hyaluronidase, the underlying CPP would become exposed
allowing for the further penetration of the liposome [228]. A number of
groups have also successfully demonstrated synergistic ef ects of using
two dif erent ligands on cell uptake [229, 230] while maintaining the
specii city of the formulation [231]. h is synergism usually results from
the multivalent binding of both the targeting ligands. h at aside, it is
important to keep in mind that employing multiple ligands can result