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

Area of Science:

• Biophysics
• Biomaterials
• Cardiovascular Research

Background:

• Red blood cells (RBCs) are explored as natural drug delivery vehicles due to their biocompatibility and circulation time.
• Targeted drug delivery to stenotic arteries remains a significant clinical challenge.

Purpose of the Study:

• To investigate the use of shear-responsive RBCs (sr-RBCs) for mechanical drug release at arterial constrictions.
• To evaluate the biophysical properties and in vivo-like behavior of sr-RBCs under flow conditions.

Main Methods:

• Engineering RBCs to be shear-responsive for controlled cargo release.
• Perfusion studies using stenotic arterial models and microfluidic capillary networks.
• Multiscale modeling of RBC suspension fluid dynamics and membrane stretching.

Main Results:

• sr-RBCs demonstrated shear-dependent drug release exclusively in constricted arterial models.
• No drug release occurred in unconstricted vessels, preserving membrane integrity and CD47 expression.
• sr-RBCs successfully navigated microvascular networks without premature cargo release.

Conclusions:

• sr-RBCs offer a targeted drug delivery mechanism triggered by mechanical forces in stenotic arteries.
• This biophysical strategy shows promise for treating vascular constrictions and related diseases.
• Mechanosensitive cell carriers represent a novel therapeutic avenue for cardiovascular conditions.