RNAi as New Class of Nanomedicines - Harnessing Biomaterials in Nanomedicine: Preparation, Toxicity, and Applications - page 171

demonstrated the feasibility of using antibodies to direct siRNAs
to specific cell populations, the cationic proteins or peptides have
a limited siRNA binding capacity (approximately 6 siRNAs/fusion
molecule).
To improve the efficiency of antibody mediated siRNA delivery,
antibodies can be attached to the surface of liposome-based
nanoparticles. The encapsulation of cyclin D1 siRNAs in lipid
nanoparticles coated on their outer surface with an anti-β 7 integrin
antibody eff ectively silenced cyclin D1 expression in gut mononuclear
leukocytes following intravenous injection [122]. The knockdown of
cyclin D1 in these cells reversed the lymphocyte proliferation and
inflammatory cytokine expression patterns associated with dextran
sodium sulfate (DSS)-induced colitis in mice. A single-chain antibody
(scAb) to the transferrin receptor, whose expression is elevated in a
wide variety of tumor types, including breast and pancreatic tumors,
facilitated the delivery of Her2 siRNAs to subcutaneously implanted
tumor cells [17]. The siRNA-mediated silencing of Her2 sensitized
the tumor cells to treatment with chemotherapeutic agents leading
to a reduction in tumor size. Zheng et al. also achieved eff ective
siRNA-mediated silencing of CD40 in dendritic cells treated with
immunoliposomes coated with anti-DEC-205 antibodies in vitro and
in vivo [164].

6.2.2 Ligand-Mediated siRNA Delivery

As an alternative to antibodies, cell type-specific delivery could be
achieved by taking advantage of the specificity of ligands, including
peptides, hormones, chemokines, sugars, and lipids, which
recognize and bind specific cell surface molecules. The conjugation
of a cholesterol molecule to the 3 ′ terminus of the passenger strand
of a siRNA targeting ApoB led to uptake of the siRNA by cells of
the liver and jujenum bearing lipoprotein receptors [138]. This
treatment resulted in decreased ApoB mRNA and protein levels
and a concomitant decrease in serum cholesterol in ApoB siRNA
treated mice compared with control siRNA treatment. In a similar
manner, cholesterol-conjugated siRNAs were used to deliver an
siRNA targeting a mutant version of the huntingtin gene to neuronal
cells. The intrastriatal injection of the cholesterol-conjugated siRNA
was able to attenuate the abnormal behavior associated with a rapid
onset model of Huntington's disease in mice [29]. The conjugation