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Monobody adapter for functional antibody display on nanoparticles for adaptable targeted delivery applications.

Published version
Peer-reviewed

Change log

Authors

Albert, C 
Bracaglia, L 
Koide, A 
DiRito, J 

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.

Description

Funder: U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID)


Funder: American Association for the Study of Liver Diseases (AASLD); doi: https://doi.org/10.13039/100005347

Keywords

Article, /631/61/350/354, /631/250/1854, /631/154/152, /13, /13/106, /13/31, /13/62, /13/1, /14/19, /14/34, /14/35, /14/63, /123, /128, article

Journal Title

Nat Commun

Conference Name

Journal ISSN

2041-1723
2041-1723

Volume Title

Publisher

Springer Science and Business Media LLC
Sponsorship
U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID) (AI132895, AI145965)
U.S. Department of Health & Human Services | NIH | NCI | Division of Cancer Epidemiology and Genetics, National Cancer Institute (National Cancer Institute Division of Cancer Epidemiology and Genetics) (CA194864)
U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) (HL157552)
U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases) (DK007276)