Targeting Ups Nanoparticle Accumulation in Graft Endothelial Cells
Targeted drug administering nanomedicines, used ex vivo, have promise.
Healthday News — Targeting can enhance accumulation of nanoparticles (NPs) to graft endothelial cells (ECs) of human kidneys undergoing ex vivo normothermic machine perfusion (NMP), according to research published in Science Translational Medicine.
Noting that short periods of NMP provide an opportunity to deliver therapeutics directly to an organ; specifically, to the vascular ECs before transplant, Gregory T. Tietjen, PhD, from Yale University in New Haven, Conn., and colleagues discuss ways to improve NP accumulation within graft ECs.
The researchers found that for human kidneys undergoing NMP, surface conjugation of an anti-CD31 antibody selectively enhanced targeting of NPs to graft ECs. Targeting enhanced EC accumulation by about 5- to 10-fold or more in discrete regions of the renal vasculature, based on a 2-color quantitative microscopy approach. Non-specific accumulation of NPs occurred within obstructed regions of the vasculature that were poorly perfused.
"These quantitative preclinical human studies demonstrate the therapeutic potential for targeted nanomedicines delivered during ex vivo NMP," the authors write.
Tietjen GT, Hosgood SA, Dirito J, et al. Nanoparticles targeting to the endothelium during normothermic machine perfusion of human kidneys. Science Translational Medicine. 2017 Nov 29. doi: 10.1126/scitranslmed.aam6764