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 .