Manipulation of Leukocytes Using Therapeutic RNAi Delivered by Targeted and Stabilized Nanoparticles - Nanotechnology for the Delivery of Therapeutic Nucleic Acids - page 183

cells are among the most challenging targets for siRNA delivery, as
these cells are resistant to conventional transfection reagents and
are dispersed in the body, making it challenging to achieve the
successful localization of siRNA to the target cells or to deliver siRNAs
passively via systemic administration. Therefore, active targeted
delivery systems are being developed, in which specific antibodies,
ligands, and ligand mimetics are used to mediate the targeting and
internalization of the siRNA payloads into cells (Fig. 8.2). Some of
these strategies have been demonstrated to deliver siRNAs into
leukocytes , including PEGylated nanoscale liposomes with

ligands that bind to receptors expressed on leukocytes covalently

in vitro

A B C

Stick

3'

siR N A

5'

Aptamer

F

E

+
+ +
+

+
+ +

D

siR N A

L i nker

CpG

G H

Figure 8.2 Targeted delivery systems for leukocytes. (A) siRNA encapsulated

in PEGylated polysome nanoparticles with ligand molecules
attached to the PEG; (B) a complex of siRNAs with the PTD-DRBD
fusion protein; (C) siRNA synthetically linked to an aptamer; (D)
siRNA synthetically conjugated to a CpG oligonucleotide; (E) an
atelocollagen-siRNA complex; (F) the 9 arginine (9R) strategy
is shown with either an I-tsNP-entrapping siRNA (G), a single-
chain variable fragment (scFv)-protamine fusion protein loaded
with siRNAs (H), or with a ligand (not shown).