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 (R2 = 0.81) but low correlation between retinal endothelial and retinal epithelial transfection (R2 = 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 EditorPolymeric 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.

A class of polymers, poly(beta-amino esters), (PBAEs) was evaluated to find polymers that can transfect both microvascular (HREC) and macrovascular (HUVEC) cells. These polymers self-assemble with DNA to form nanoparticles (right). Certain PBAEs were able to transfect both of these types of cells with high efficiency (left), better than the leading commercially available reagents. Additionally, there is a strong correlation between the transfection profiles of these endothelial type cells (R2 = 0.81). This contrasts with a much lower correlation between the transfection profiles of the human retinal endothelial cells and human retinal pigment epithelial cells (R2 = 0.21).Figure optionsDownload high-quality image (436 K)Download as PowerPoint slide