Monobody adapter for functional antibody display on nanoparticles for adaptable targeted delivery applications.
C AlbertL BracagliaA KoideJ DiRitoTaras LysyyL HarkinsC EdwardsO RichfieldJulian GrundlerK ZhouE DenbaumGayatri KetavarapuT HattoriS PerincheriJ LangfordAlborz FeiziD HaakinsonS A HosgoodM L NicholsonJ S PoberW Mark SaltzmanShohei KoideGregory T TietjenPublished in: Nature communications (2022)
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.
Keyphrases
- endothelial cells
- cancer therapy
- high glucose
- drug delivery
- vascular endothelial growth factor
- pluripotent stem cells
- induced pluripotent stem cells
- magnetic resonance imaging
- high throughput
- small molecule
- emergency department
- computed tomography
- binding protein
- reactive oxygen species
- transcription factor
- walled carbon nanotubes
- climate change