biostudies-literatureAlbert CNCATS NIH HHSU.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious DiseasesNIAID NIH HHSNHLBI NIH HHSU.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood InstituteU.S. Department of Health & Human Services | NIH | NCI | Division of Cancer Epidemiology and Genetics, National Cancer InstituteKidney Research UKNIDDK NIH HHSAmerican Association for the Study of Liver DiseasesNational Institute for Health Research (NIHR)NCI NIH HHSNIH HHSNIGMS NIH HHSU.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases5998https://www.ebi.ac.uk/biostudies/studies/S-EPMC9553936biostudies-literatureUnknown13(1)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 tranNature communicationsMonobody adapter for functional antibody display on nanoparticles for adaptable targeted delivery applications.PMC9553936T32 AI155387NIHR203332NIHR201350U01 AI132895T32 DK007276AI145965DK007276UL1 TR001863IN6/2012HL157552R01 CA194864CA194864T32 GM145452K99 HL157552U01 AI145965R00 HL157552AI132895S10 OD023603Harkins LPerincheri SSaltzman WMHattori TDiRito JPober JSTietjen GTKoide SLangford JRichfield OEdwards CDenbaum EHaakinson DKoide AFeizi AHosgood SABracaglia LGrundler JLysyy TKetavarapu GNicholson MLAlbert CZhou KfalseMonobody adapter for functional antibody display on nanoparticles for adaptable targeted delivery applications.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 tran2022-01-01T00:00:00Z2022 Oct2026-05-27T19:10:35.511Z2025-02-19T03:22:55.434ZS-EPMC95539363622081710.1038/s41467-022-33490-8