Heparin-Binding Proteins in the Nanoparticle Corona Enhance Cellular Uptake through Glycocalyx Interactions.

ABSTRACT: Nanoparticles (NPs) designed for intracellular delivery must first navigate the cell-surface glycocalyx before reaching the plasma membrane for internalization. Here, we hypothesized that the glycocalyx can both hinder NP uptake via a barrier effect and enhance uptake by providing recognition sites for corona proteins. To dissect these opposing mechanisms, we prepared NPs with plasma protein coronas either enriched or depleted in heparin-binding proteins (HBPs), along with model coronas containing selected HBPs or non-HBPs. Biophysical assays confirmed strong heparin interactions for HBP-rich NPs, whereas HBP-poor NPs showed weak or no binding. To assess the role of corona-glycocalyx interactions in NP uptake, we used glycocalyx-depleted cells, a chemical inhibitor, and heparin and antithr

SUBMITTER: Olivieri PH 

PROVIDER: S-EPMC12756911 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature