Probing cell-nanoparticle (cubosome) interactions at the endothelial interface: do tissue dimension and flow matter?

Area of Science:

• Nanomedicine and Biomaterials Science
• Cellular and Molecular Biology
• Biophysics and Bioengineering

Background:

• Biomimetic cellular models are crucial for predicting nanoparticle behavior in vivo.
• Understanding nanostructured lipid-based particles (cubosomes) interactions with vascular cells is key for biomedical applications.
• Conventional 2D cell cultures may not accurately represent complex in vivo vascular environments.

Purpose of the Study:

• To evaluate the biointeractions of cubosomes with human vascular cells.
• To investigate the influence of tissue dimension (2D vs. 3D) and shear flow on these interactions.
• To assess the impact of cubosomes on endothelial cell-cell junctions under dynamic flow conditions.

Main Methods:

• Development of a 3D dynamic tubular endothelial construct in a glass capillary.
• Simulation of static, venous (0.8 dynes/cm²), and arterial (10 dynes/cm²) shear flow conditions.
• Quantification of cell-cubosome association and analysis of PECAM-1 immunoexpression.

Main Results:

• Cell-cubosome association was similar in 2D and 3D models without flow.
• Flow conditions significantly reduced cubosome association: 50% decline under venous flow and 98% under arterial flow.
• Cubosomes minimally affected cell-cell contact (PECAM-1 expression unchanged) but showed different distribution patterns in 2D vs. 3D models.

Conclusions:

• Tissue dimension and shear flow are critical factors governing nanoparticle-cell interactions.
• Dynamic 3D vascular models with flow are essential for realistic assessment of nanoparticle bio-nano behavior.
• Shear-guided interactions significantly influence the fate of non-targeted nanoparticles in circulation.