Nanoparticle Properties Influence Transendothelial Migration of Monocytes

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Neuroscience

Background:

• Nanoparticle drug delivery to the brain is hindered by the blood-brain barrier (BBB).
• Monocytes can cross the BBB, offering a potential cell-based delivery route.
• Optimizing nanoparticle design is crucial for effective monocyte-mediated BBB transport.

Purpose of the Study:

• To investigate how nanoparticle design parameters influence monocyte association and transport across the BBB.
• To compare the efficacy of synthetic protein nanoparticles (SPNPs) versus polymeric nanoparticles for monocyte-mediated BBB delivery.

Main Methods:

• Electrohydrodynamic jetting was used to create nanoparticles of varying sizes, compositions, and elasticity.
• An in vitro human BBB model using human cerebral microvascular endothelial cells (hCMEC/D3) was developed.
• THP-1 monocyte uptake and migration across the BBB model were assessed for different nanoparticle types.

Main Results:

• Synthetic protein nanoparticles (SPNPs), specifically human transferrin (TF) and human serum albumin (HSA), enhanced monocyte-mediated BBB transport compared to polymeric nanoparticles.
• 200 nm TF SPNPs showed high monocyte association (138 particles/cell).
• Monocyte migration increased 2.1-2.3 fold with SPNP loading, linked to upregulated migration genes like integrin subunits.

Conclusions:

• SPNPs demonstrate potential as effective platforms for drug and/or gene delivery across the BBB via monocytes.
• TF and HSA SPNPs offer advantages over conventional polymer nanoparticles for monocyte-mediated brain delivery.