Dual conjugation of magnetic nanoparticles with antibodies and siRNA for cell-specific gene silencing in vascular cells

RNA therapy is a rapidly expanding field and has great promise in achieving targeted gene silencing and contributing to personalized medicine. However, the delivery of RNA molecules into targeted organs or cells is still challenging. To overcome this hurdle, a number of nanocarriers with pros and cons have been developed. This study was designed to develop a simple and cost-effective approach to functionalize biodegradable magnetic iron nanoparticles (MNPs) for cell-specific siRNA delivery. MNPs were synthesized based on co-precipitation and further functionalized with sodium citrate and polyethyleneimine (PEI) followed by material characterization using TEM, FTIR, and Zeta potential. The citrate and PEI-coated MNPs were further conjugated with CD31 antibody and complexed with siRNA using a linker-free approach. siRNA-loaded MNPs successfully knocked down the expression of <i>GAPDH</i> in human endothelial cells (ECs) and <i>NOTCH3</i> in human vascular smooth muscle cells (VSMCs). In an EC and VSMC co-culture system under shear stress to mimic blood flow, siRNA and CD31 conjugated MNPs specifically targeted and delivered siRNA into the ECs. Our approach represents a versatile platform that could be adopted for targeted general siRNA delivery.