Antibodies
Monoclonal antibodies and their
fragments have been widely used for treatment and diagnosis of various
diseases (Suurs, Lub-de Hooge, de Vries, & de Groot, 2019).
Antibody-based deliveries offer a robust strategy to develop novel
specific ligand-coupled nanoparticle systems for siRNA delivery
(Kulhari, Jangid, & Adams, 2019). The antibody structure can be
categorized into two distinct biofunctional parts. The crystallizable
fragment (Fc) binds to Fc receptor on the membrane of the immune cell or
other antibodies and the
antigen-binding fragment (Fab)
mediates antigen recognition via complementarity-determining regions.
Fab fragments are useful components for decreasing the size of
antibodies (around 15 nm), and thus reducing immunogenicity and
increasing the pharmacokinetic profile of nanoparticle-based drug
delivery systems (Warram et al., 2014).
Human tissue factors (TFs) are overexpressed in pancreatic cancer cells.
Thus, anti-human TF can be used to increase the efficacy of delivery
(Chen et al., 2014). Min et al . (Min et al., 2018) developed
polyion complex (PIC) micelles which were composed of a copolymer of
azide-functionalized polyethylene glycol and poly-L-Lysine and further
modified with anti-human tissue factor (TF) in order to deliver PLK1
siRNA into the pancreatic cancer BxPC3 cells. Gene silencing activity
against PLK1 mRNA in cancer cells was the most significant in the
3(Fab′)-micelle. Moreover, a higher penetrability and the cellular
internalization amount in BxPC3 spheroid was observed with the
3(Fab′)-micelle compared with one or two molecule(s) of Fab′-conjugated
PIC micelles.
Li et al. (Li et al., 2016) designed Iron oxide nanoparticles
(IONPs)-PEI delivery system modified with anti-human CD44v6 single-chain
variable fragment (scFvCD44v6) to transfer GEM and siRNA
targeting Bmi-1 (B-cell-specific Moloney murine leukemia virus insertion
site 1) which play important roles in proliferation, survival, and
invasion of pancreatic tumor cells. The
GEM-scFv-IONP-PEI/siBmi-1
structure shows a synergistic anti-pancreatic tumor effect not onlyin vitro but also in vivo .