Multifactorial determinants that govern nanoparticle uptake by human endothelial cells under flow

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Cell Biology

Background:

• Vascular endothelium plays a crucial role in pathological processes like inflammation and atherosclerosis.
• Endothelial cells are constantly exposed to mechanical forces from blood flow (shear stress).
• Nanoparticles are being explored for therapeutic delivery, but their interaction with endothelial cells needs optimization.

Purpose of the Study:

• To investigate the impact of shear stress on nanoparticle uptake by endothelial cells.
• To evaluate how inflammatory conditions affect nanoparticle-endothelial cell interactions.
• To understand the role of cytoskeletal changes in nanoparticle internalization.

Main Methods:

• Utilized microfluidic channels to expose cultured endothelial cells to quantum dots and silica nanoparticles under varying shear stress (SS) rates (0.05, 0.1, 0.5 Pa).
• Simulated vascular inflammation using tumor necrosis factor-α (TNF-α) and cell membrane damage with Triton X-100.
• Employed atomic force microscopy to analyze cytoskeletal rearrangements.

Main Results:

• Shear stress critically enhances nanoparticle uptake, with maximum uptake observed at 0.05 Pa.
• Neither TNF-α treatment nor Triton X-100 significantly altered nanoparticle uptake.
• Increased actin-based cytoskeletal structures (stress fibers, membrane ruffles) were observed, correlating with endocytosis.

Conclusions:

• Shear stress is a dominant factor governing nanoparticle uptake by endothelial cells.
• Nanoparticle delivery strategies must consider shear stress, endothelial cell state, and nanoparticle properties.
• Optimizing nanoparticle-drug conjugates for parenteral delivery requires understanding these combined effects.