Pretargeted delivery of PEG-coated drug carriers to breast tumors using multivalent, bispecific antibody against polyethylene glycol and HER2

Publication date: Available online 5 August 2019Source: Nanomedicine: Nanotechnology, Biology and MedicineAuthor(s): Christina L. Parker, Morgan D. McSweeney, Andrew T. Lucas, Timothy M. Jacobs, Daniel Wadsworth, William C. Zamboni, Samuel K. LaiAbstractPretargeting is an increasingly explored strategy to improve nanoparticle targeting, in which pretargeting molecules that bind both selected epitopes on target cells and nanocarriers are first administered, followed by the drug-loaded nanocarriers. Bispecific antibodies (bsAb) represent a promising class of pretargeting molecules, but how different bsAb formats may impact the efficiency of pretargeting remains poorly understood, in particular Fab valency and Fc receptor (FcR)-binding of bsAb. We found the tetravalent bsAb markedly enhanced PEGylated nanoparticle binding to target HER2+ cells relative to the bivalent bsAb in vitro. Pretargeting with tetravalent bsAb with abrogated FcR binding increased tumor accumulation of PEGylated liposomal doxorubicin (PLD) 3-fold compared to passively targeted PLD alone, and 5-fold vs pretargeting with tetravalent bsAb with normal FcR binding in vivo. Our work demonstrates that multivalency and elimination of FcRn recycling are both important features of pretargeting molecules, and further supports pretargeting as a promising nanoparticle delivery strategy.Graphical AbstractPretargeting is an alternative nanoparticle delivery approach used to overcome limitations associated with passive an...
Source: Nanomedicine: Nanotechnology, Biology and Medicine - Category: Nanotechnology Source Type: research