Gene delivery nanoparticles specific for human microvasculature and macrovasculature.

Endothelial cell dysfunction is a critical component of ocular diseases such as age-related macular degeneration and diabetic retinopathy. An important limitation in endothelial cell research is the difficulty in achieving efficient transfection of these cells. A new polymer library was here synthesized and utilized to find polymeric nanoparticles that can transfect macrovascular (human umbilical vein, HUVECs) and microvascular (human retinal, HRECs) endothelial cells. Nanoparticles were synthesized that can achieve transfection efficiency of up to 85% for HRECs and 65% for HUVECs. These nanoparticle systems enable high levels of expression while avoiding problems associated with viral gene delivery. The polymeric nanoparticles also show cell-specific behavior, with a high correlation between microvascular and macrovascular transfection (R(2) = 0.81) but low correlation between retinal endothelial and retinal epithelial transfection (R(2) = 0.21). These polymeric nanoparticles can be used in vitro as experimental tools and potentially in vivo to target and treat vascular-specific diseases. FROM THE CLINICAL EDITOR: Polymeric nanoparticles were synthesized with the goal of transfecting endothelial cells, which are commonly considered difficult targets. The authors report excellent transfection efficiency of up to 85% for human retinal and 65% for human umbilical vein endothelial cells. These NPs can be used in vitro as experimental tools and potentially in vivo to target and treat vascular-specific diseases.