Monobody adapter for functional antibody display on nanoparticles for adaptable targeted delivery applications
Claire Albert, Laura G. Bracaglia, Akiko Koide, Jenna DiRito, Taras Lysyy, Lauren Harkins, Christopher M. Edwards, O. Richfield, Julian Grundler, Kristal Zhou, Eric Denbaum, Gayatri Ketavarapu, Takamitsu Hattori, S. Perincheri, John Langford, Alborz Feizi, Danielle J. Haakinson, Sarah A. Hosgood, Michael L. Nicholson, Jordan S. Pober, W. Mark Saltzman, Shohei Koide, Gregory T. Tietjen
Abstract
Vascular endothelial cells (ECs) play a central role in the pathophysiology of many diseases. The use of targeted nanoparticles (NPs) to deliver therapeutics to ECs could dramatically improve efficacy by providing elevated and sustained intracellular drug levels. However, achieving sufficient levels of NP targeting in human settings remains elusive. Here, we overcome this barrier by engineering a monobody adapter that presents antibodies on the NP surface in a manner that fully preserves their antigen-binding function. This system improves targeting efficacy in cultured ECs under flow by >1000-fold over conventional antibody immobilization using amine coupling and enables robust delivery of NPs to the ECs of human kidneys undergoing ex vivo perfusion, a clinical setting used for organ transplant. Our monobody adapter also enables a simple plug-and-play capacity that facilitates the evaluation of a diverse array of targeted NPs. This technology has the potential to simplify and possibly accelerate both the development and clinical translation of EC-targeted nanomedicines.