Skip Navigation

Publication Detail

Title: Engineering Polymer-Binding Bispecific Antibodies for Enhanced Pretargeted Delivery of Nanoparticles to Mucus-Covered Epithelium.

Authors: Huckaby, Justin T; Parker, Christina L; Jacobs, Tim M; Schaefer, Alison; Wadsworth, Daniel; Nguyen, Alexander; Wang, Anting; Newby, Jay; Lai, Samuel K

Published In Angew Chem Int Ed Engl, (2019 Apr 16)

Abstract: Mucus represents a major barrier to 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. In this work, 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, thereby 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 PEGylated particles binding to cells by around 2-fold or more compared to either non-targeted or actively targeted PEGylated 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.

PubMed ID: 30811861 Exiting the NIEHS site

MeSH Terms: Antibodies, Bispecific/metabolism*; Humans; Nanoparticles/metabolism*; Polymers/metabolism*

Back
to Top