Nanoparticle targeting during ex vivo perfusion of human kidney: A new quantitative approach to defining the principles of targeting in situ

Polymeric nanoparticles can be used as drug delivery vehicles with the capacity to act as slow release therapeutic depots in the treatment of a wide variety of diseases. Molecular targeting (e.g. via surface conjugation of antibodies) has emerged as a strategy to ensure that the particles have specificity for the anatomic location and cellular subtype of greatest clinical need. Unfortunately several studies and multiple clinical trials have demonstrated we don’t yet know how to translate robust targeting in a petri dish into a effective therapeutic for a person. This is largely due to the fact that we lack a theoretical understanding of the conditions necessary to ensure maximal targeting benefit in a complex in vivo environment. In this talk, I will describe our recent efforts to leverage ex vivo perfusion of human kidney (a newly developed clinical technique in organ transplant used to resuscitate marginal organs) to quantitatively define nanoparticle targeting specificity and kinetics in a experimentally viable human organ that was declined for transplant. In addition to hastening new therapeutic paradigms in clinical organ transplant, we believe these results can provide new insights for the engineering of nanomedicines capable of anatomic precision after systemic administration.