Nanosized Drug Delivery Vectors and the Reticuloendothelial System - Intracellular Delivery: Fundamentals and Applications - page 169

macrophages and avoidance of other cell types. Thus, although targeting to RES
macrophages can be achieved by the administration of nanomedicines containing
the agent of interest that are readily opsonised and endocytosed, the use of targeting
ligands can achieve this effect for non-RES targeted particles that otherwise have
been optimized for the proposed delivery.
Macrophage targeting ligands are specifically ligands to receptors that are ether
specifically or over-expressed on the surface of the target macrophages. In addition
to targeting towards the specific cells that make up the RES, other ligands may be
used to enhance the delivery and cellular internalization of materials to other cells
within organs of the RES, such as hepatocytes. Galactose is an example of a hepa-
tocyte targeting ligand. This section, however, is focused specifically on the tar-
geted delivery of particles to reticuloendothelial cells (specifically the macrophages).
Table 1 summarizes the different ligands and their target receptors that have been
used to improve nanomedicine targeting towards macrophages.
Phosphatidylserine is commonly incorporated into liposomes to decrease the
surface charge of the colloid or to effect targeting towards macrophages. In mice,
targeting of phosphatidylserine liposomes to liver Kupffer cells occurs without the
need for prior opsonisation by plasma components (Liu and Liu 1996 ). However,

Table 1 Ligands used to improve targeting of nanoparticles towards reticuloendothelial organs
and macrophages and the target receptors
Ligand Receptor Conjugated nanomedicine References

Phosphatidylserine TIM-4, stablin-1

& 2, BAI-1
plus others

Liposomes Liu et al. ( 1995a )

Mannose/mannan Mannose receptors

(multiple sub-
types)

Liposomes, dendrimers,
nanoparticles, niosomes,
antigens. micelles, metal
colloids, emulsions

Nag and Ghosh
( 1999 ); Kaur
et al. ( 2008 );
Vyas et al.
( 2000 ); Irache
et al. ( 2008 )

RVG peptide Nicotinic

acetylcholine
receptor

RVG peptide-siRNA Kim et al. ( 2010 )

Stromal cell derived
factor 1

CXCR4 Peptide-DNA complex Egorova et al.

( 2009 )

Anti-HLA-DR HLA-DR Liposomes Dufresne et al.

( 1999 )

N-formyl-methionyl
leucyl
phenylalanine

Formyl peptide
receptor 1

Nanoparticle, liposomes Wan et al. ( 2008 );

Morikawa et al.
( 1988 )

Fc region of antibody Fc receptor Opsonised nanomedicines

Decadeoxyguanine Scavenger receptor

class 1

Liposomes Rensen et al. ( 2006 )

Tuftsin Tuftsin receptor

(uncloned)

Dendrimer, liposomes Dutta et al. ( 2008 );

Agarwal et al.
( 1994 )