Engineering polymer‐binding bispecific antibodies for enhanced pretargeted delivery of nanoparticles to mucus‐covered epithelium

Mucus represents a major barrier precluding sustained and targeted drug delivery to mucosal epithelium. Ideal drug carriers should not only rapidly diffuse across mucus, but also bind the epithelium. Unfortunately, ligand‐conjugated particles often exhibit poor penetration across mucus. Here, we explored a two‐step "pretargeting" approach through engineering a bispecific antibody that binds both cell‐surface ICAM‐1 and polyethylene glycol (PEG) on the surface of nanoparticles, effectively decoupling cell targeting from particle design and formulation. When tested in a mucus‐coated Caco‐2 culture model that mimics the physiological process of mucus clearance, pretargeting increased the amount of PEG‐particles binding to cells by ~2‐fold or more compared to either non‐targeted or actively targeted PEG‐particles. Pretargeting also markedly enhanced particle retention in mouse intestinal tissues. Our work underscores pretargeting as a promising strategy to improve the delivery of therapeutics to mucosal surfaces.

from A via a.sfakia on Inoreader https://ift.tt/2Ss79bL