Avidity-by-design: spatial control of T7 peptide presentation on polymersomes dictates blood–brain barrier transport fate

In short

The transferrin receptor is a popular way into the brain. But ligands aimed at it compete with transferrin itself, and the carriers they bring in are often trafficked the wrong way.

This paper builds a library of pH-responsive polymersomes carrying the T7 peptide. It varies two things: how many ligands each particle carries, and how deep they sit in the PEG corona. That depth turns out to decide where the particles go. With fully exposed ligands they cross brain endothelial cells; with partly buried ones they stay in the endothelium.

Unlike LRP1-targeted carriers, this transport does not rely on PACSIN2. The result is a design rule, avidity by design, for building carriers that either cross the barrier or stay at the vessel wall.

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© The authors, 2026. Open access under CC BY 4.0; shared here unchanged.