Controlling Nanoparticle Uptake in Innate Immune Cells with Heparosan Polysaccharides.

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Immunology

Background:

• Targeted delivery of nanoparticles to immune cells is crucial for therapeutic applications.
• Heparosan (HEP) polysaccharides offer a potential surface modification for controlling nanoparticle-cell interactions.

Purpose of the Study:

• To investigate the use of HEP-coated nanoparticles for controlled delivery to innate immune cells.
• To elucidate the mechanisms of nanoparticle uptake and intracellular trafficking.

Main Methods:

• Coating nanoparticles with heparosan (HEP) polysaccharides.
• Assessing nanoparticle endocytosis by innate immune cells using various pathways (clathrin-mediated, macropinocytosis).
• Quantifying cellular uptake via systematic variation of HEP surface density.

Main Results:

• HEP-coated nanoparticles were endocytosed by innate immune cells in a time-dependent manner.
• Uptake pathways involved clathrin-mediated endocytosis and macropinocytosis.
• Nanoparticle uptake was controllable over 3 orders of magnitude by adjusting HEP surface density.
• Evidence of nanoparticle escape from intracellular vesicles into the cytoplasm was observed.

Conclusions:

• HEP-coated nanoparticles demonstrate significant potential for targeting innate immune cells.
• This technology enables efficient intracellular delivery, including cytoplasmic access.
• HEP nanoparticle surface engineering is a promising platform for drug/gene delivery and immuno-engineering.