Engineering Polymer‐Binding Bispecific Antibodies for Enhanced Pretargeted Delivery of Nanoparticles to Mucus‐Covered Epithelium

Autor: Alexander K. Nguyen, Daniel Wadsworth, Samuel K. Lai, Timothy M. Jacobs, Alison Schaefer, Jay M. Newby, Anting Wang, Christina L. Parker, Justin T. Huckaby
Rok vydání: 2019
Předmět:
Zdroj: Angewandte Chemie. 131:5660-5664
ISSN: 1521-3757
0044-8249
DOI: 10.1002/ange.201814665
Popis: 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.
Databáze: OpenAIRE
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