(718c) Using Shape Effects to Enhance Nanoparticle Targeting to Lungs and Brain

Polymeric drug delivery systems have broad applications for targeted drug delivery and treatment of a variety of diseases. Currently, low targeting efficacy and side effects from off target accumulation have limited utility of nanocarriers.  Here, we report, based on a mathematical mode, in vitro, and in vivo studies, that endothelial targeting can be enhanced by simply engineering the shape of antibody carrying nanocarriers.  Microfluidic systems (Synthetic Microvasculature Networks) were used to mimic the vasculature and show that rod shaped (nanorods) particles, as opposed to their spherical counterparts (nanospheres), exhibit higher specific and lower non-specific accumulation under flow conditions at target sites.  Enhanced nanorod binding was supported by a mathematical model of particle-surface interactions describing the polyvalent interactions and hindrance of entropic losses which contribute to improved binding of nanorods.  Further, shape dependent enhancement of vascular targeting was validated in vivo by showing improved targeting of nanorods, compared to nanospheres, conjugated with endothelial antibodies targeting lungs (anti-ICAM-1) and brain (anti-transferrin-receptor).  These results highlight the efficacy of nanorods in providing targeted delivery to vascular endothelium for treatment of cancer, cardiovascular diseases, and inflammation.