High-throughput 3D visualization of nanoparticles attached to the surface of red blood cells

Blood circulation is the main distribution route for systemic delivery and the possibility to manipulate red blood cells (RBCs) by attaching nanoparticles to their surface provides a great opportunity for cargo delivery into tissues. Nanocarriers attached to RBCs can be delivered to specific organs orders of magnitude faster than if injected directly into the bloodstream. Another advantage is a shielding from recognition by the immune system, thereby increasing the efficiency of delivery. We present a high-throughput microfluidic method that can monitor the shape of drifting cells due to interactions with nanoparticles and characterize the 3D dispersion of fluorescent silica nanoparticles at the surface of RBCs. The combination of fluorescence microscopy with image analysis demonstrates that the adsorption of silica nanoparticles onto the surface of RBCs is strongly influenced by electrostatic interactions. A reduced number of intact RBCs with increasing nanoparticle concentration beyond a certain threshold points to a toxicity mechanism associated with the nanoparticle adsorption at the surface of RBCs.