The Potential and Current Progress of Internalizing Molecules in Targeted Drug Delivery - Intracellular Delivery: Fundamentals and Applications - page 104

against the cellular CCR5 co-receptor and two conserved HIV-1 genes ( vif and tat )
was loaded into scFvCD7-9R system, subsequently was systemically administered
to HIV-1 infected animal model. The weekly injection resulted in suppression of
HIV-1 infection and protection of CD4+ T cell depletion in humanized mice.

3.1.4 Anti-HIV gp120 Antibody

The interaction of the HIV envelope glycoprotein gp120 with the cellular CD4
receptor is a crucial step in the entry of HIV into T-cells (Ugolini et al. 1999 ;
Sattentau and Moore 1993 ). HIV gp120 is exposed on the surface of virus particles
and the plasma membrane of HIV-1 infected cells. Therefore, it represents an excel-
lent marker to distinguish HIV-1 infected host cells from non-infected cells (Kwong
et al. 1998 ). F105, an anti-HIV gp120 monoclonal antibody, has been demonstrated
to bind with high affinity to its ligand gp120 expressed on the surface of a wide
range of HIV-1 laboratory strains and primary isolates (Posner et al. 1991 ).
Importantly, its selective binding to HIV-1 infected cells triggers rapid cellular
internalization. Thus, F105 has the potential to be an excellent internalizing molecule
for selective drug delivery to HIV-1 infected cells (Clayton et al. 2007 ). Song et al.
have successfully applied a heavy chain fragment of F105 to increase receptor-
specific uptake to cells expressing the HIV envelope protein (Song et al. 2005 ). In
this system, the F105 antibody fragment - protamine fusion protein was able to
specifically bind to and deliver siRNAs to HIV-infected primary T cells or HIV
envelope-expressing cells. Moreover, their results demonstrated that the siRNA
targeting the HIV-1 gag capsid gene delivered by such a fusion protein inhibited
HIV-1 replication only in cells expressing the HIV-1 envelope. Recently, PEGylated
liposomes coated with a F105 Fab' fragment have been developed and evaluated for
targeted delivery of a novel HIV-1 protease inhibitor PI1 (Clayton et al. 2009 ). The
anti-HIV immunoliposomes were selectively taken up by HIV-1 infected cells.
When compared with free drug or non-targeted drug, the targeted PI1 delivery
showed a greater inhibitory effect on viral replication.

3.2 Protein-Mediated Drug Delivery

3.2.1 Transferrin and Lactoferrin

Transferrin (Tf), an 80 kDa glycoprotein that transports iron into cells, is one of
most popular tumor targeting ligands, because its receptors (TfRs) are over-
expressed in many types of cancer cells and TfR expression is correlated with the
proliferation and malignancy of the tumor cells (Daniels et al. 2006 ). After interac-
tion of Tf-TfR, Tf is internalized into cells through an endocytosis pathway (Qian
et al. 2002 ). To date, numerous investigations have demonstrated that Tf-conjugated
nanocarriers loaded with various drugs (e.g. anticancer agents, oligonucleotides,
therapeutic genes, siRNAs) could facilitate specific cellular uptake and enhance the