Cell-surface glycosaminoglycans regulate the cellular uptake of charged polystyrene nanoparticles

Area of Science:

• Biomedical Engineering
• Cell Biology
• Nanotechnology

Background:

• Nanoparticle interaction with cell surfaces is crucial for cellular uptake.
• The role of cell-surface glycosaminoglycans (GAGs) in nanoparticle internalization is not well understood.

Purpose of the Study:

• To investigate how cell-surface GAGs regulate the cellular entry of engineered nanoparticles.
• To elucidate the mechanisms of nanoparticle uptake influenced by GAGs.

Main Methods:

• Utilized Chinese hamster ovary cells and anionic/cationic polystyrene nanoparticles (PS NPs).
• Investigated nanoparticle uptake with and without enzymatic shedding of surface GAGs (heparan sulfate and chondroitin sulfate).
• Analyzed internalization pathways including clathrin-mediated endocytosis, lipid raft/cholesterol-dependent mechanisms, and macropinocytosis.

Main Results:

• Surface GAGs act as a charge-based barrier to anionic PS NP internalization.
• Cationic PS NPs show favorable interaction with GAGs and efficient internalization.
• Anionic PS NP uptake increased upon GAG shedding, while cationic PS NP uptake decreased, particularly when heparan sulfate was cleaved.
• Heparan sulfate acts as an anchor for cationic nanoparticle cellular entry.

Conclusions:

• Cell-surface GAGs significantly modulate nanoparticle cellular uptake based on surface charge.
• Heparan sulfate is identified as a key receptor facilitating cationic nanoparticle internalization.
• Findings advance understanding of nanoparticle endocytosis and inform nanocarrier design for drug delivery.