Glycocalyx Interactions Modulate the Cellular Uptake of Albumin-Coated Nanoparticles

Area of Science:

• Nanomedicine
• Biomaterials Science
• Cellular Biology

Background:

• Albumin-based nanoparticles (ABNPs) are versatile drug carriers.
• Understanding ABNP-cell interactions is key to optimizing drug delivery.
• The cellular glycocalyx's role in ABNP uptake is largely unexplored.

Purpose of the Study:

• To investigate the influence of the cellular glycocalyx on albumin-based nanoparticle (ABNP) uptake.
• To elucidate the role of albumin-glycosaminoglycan (GAG) interactions in ABNP cellular internalization.
• To assess the therapeutic potential of modulating these interactions for cancer treatment.

Main Methods:

• Utilized silica nanoparticles coated with native, cationic, and anionic bovine serum albumin (BSA).
• Employed techniques including fluorescence anisotropy, DLS, microscale thermophoresis, SPR, and computer simulations.
• Conducted uptake studies in Chinese hamster ovary (CHO) cells with varying GAG expression and enzymatic treatments.

Main Results:

• BSA and cationic BSA (BSA+) interacted with heparin (a GAG), while anionic BSA (BSA-) did not.
• The glycocalyx enhanced uptake of BSA and BSA+ coated NPs but hindered BSA- NP uptake.
• Targeting albumin-GAG interactions increased paclitaxel-induced cancer cell death.

Conclusions:

• The cellular glycocalyx critically modulates albumin-based nanoparticle uptake.
• Albumin-GAG interactions can be leveraged to enhance ABNP drug delivery efficacy.
• These findings provide a basis for rational design of improved albumin-based nanomedicines.