Modulating LRP1 and LRP8 in the blood–brain barrier using multivalent nanomedicines

Abstract

The blood–brain barrier governs the movement of misfolded proteins into and out of the central nervous system. Two receptors stand out: LRP1, and LRP8 — also known as apolipoprotein E receptor 2. Much of the evidence points to LRP1 as the main shuttle for amyloid-β.

To drive that process we formulate functionalised polymeric nanoparticles whose avidity, built from many individual ligand–receptor affinities, reproduces what happens in vivo. Alongside that we measure expression of the genes involved in transcytosis and characterise our in vitro barrier model in detail.

Both are groundwork for the real question: whether polymeric nanoparticles can improve amyloid-β clearance from the brain.

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