Shear-Responsive Red Blood Cell Carriers for Targeted Drug Delivery to Constricted Arteries.

Red blood cells (RBCs) are widely utilized as natural drug delivery systems due to their unique mechanical properties, which enable prolonged circulation and physiological function. This study examines a biophysical strategy that employs shear-responsive RBC (sr-RBC) carriers to mechanically release drugs at stenotic arteries. Intracellularly loaded sr-RBCs exhibited shear-dependent cargo release when perfused through stenotic arterial models, while no release was observed in unconstricted vessels. Notably, the sheared sr-RBCs retained their membrane integrity and CD47 expression while maintaining their ability to traverse microvascular networks without release when perfused through a microfluidic model simulating pulmonary capillaries. Multiscale modelling of RBC suspension fluid dynamics demonstrates a strong positive correlation between the sr-RBC drug release and the overall RBC membrane stretching induced by the high shear rates at various stenotic percentages. Sr-RBCs and mechanosensitive cell carriers may enable new avenues for treating life-threatening arterial constrictions and other vascular diseases.