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ApoE Protein Corona Enhances Peptide-Modified Nanoparticle Brain Delivery

RPEP-152362026Guerrero, Simón; Hassan, Natalia; Salas-Huenuleo, Edison; Moglia, Italo; Prades, Roger; Massa, Solange; Teixido, Meritxell; Guzman, Fanny; Giralt, Ernest; Albericio, Fernando; de Oliveira, Eliandre; Araya, Eyleen; Kogan, Marcelo J
evidence
The takeaway

Apolipoprotein E enrichment in the protein corona of peptide-modified nanoparticles enhanced blood-brain barrier transport through receptor-mediated transcytosis.

Corona as a tool

The blood protein coating on peptide-modified nanoparticles actually helps them cross the BBB through ApoE receptor-mediated transport

What the researchers found

Peptide-modified nanoparticles acquired ApoE-enriched protein coronas that enhanced BBB transcytosis through receptor-mediated transport, improving brain drug delivery.

Why it matters

Brain drug delivery is the biggest barrier for treating neurological diseases. Exploiting the natural ApoE transport pathway could dramatically improve brain targeting.

How the study worked

Protein corona characterization of peptide-modified nanoparticles in blood, BBB transport assays, mechanism determination, and brain biodistribution studies.

What this study cannot tell us

Preclinical studies. Human protein corona composition may differ. Long-term safety of repeated NP brain delivery unknown.

How to read the evidence

Mechanistic study with transport and biodistribution validation. Novel insight for brain-targeting nanoparticle design.

When this study was published

Published in 2025.

The bigger picture

The protein corona — once seen as a problem for nanomedicine — is revealed as a tool that can be harnessed for brain-targeted delivery through peptide surface design.

Questions still open

  • Can the protein corona composition be precisely controlled through peptide design?
  • Would this approach work for large molecule therapeutics?
  • Does ApoE genotype affect brain delivery efficiency?

Common questions

How do nanoparticles cross into the brain?
When peptide-modified nanoparticles enter the blood, they get coated with blood proteins — especially ApoE. The brain has ApoE receptors that pull these coated nanoparticles through the blood-brain barrier, delivering drugs inside.
Why is this important for brain diseases?
Most drugs can't cross the BBB. By designing nanoparticles that attract ApoE coating, researchers can piggyback on the brain's own import system to deliver medications for Alzheimer's, Parkinson's, and other brain diseases.

Read the original research

Apolipoprotein E-enriched protein corona enhances the blood-brain barrier transport of β-sheet-breaker peptide-functionalized gold nanoparticles.

Colloids and surfaces. B, Biointerfaces, 262, 115538

View on PubMed ↗Publisher’s paper ↗

Citation

Guerrero, Simón; Hassan, Natalia; Salas-Huenuleo, Edison; Moglia, Italo; Prades, Roger; Massa, Solange; Teixido, Meritxell; Guzman, Fanny; Giralt, Ernest; Albericio, Fernando; de Oliveira, Eliandre; Araya, Eyleen; Kogan, Marcelo J. (2026). Apolipoprotein E-enriched protein corona enhances the blood-brain barrier transport of β-sheet-breaker peptide-functionalized gold nanoparticles.. Colloids and surfaces. B, Biointerfaces, 262, 115538. https://doi.org/10.1016/j.colsurfb.2026.115538