# Selective Membrane Protein Enrichment Enables Defined Biomimetic Nanoparticles for Endothelial Targeting

## TL;DR

This paper introduces a new type of biomimetic nanoparticle with specific proteins that better target inflamed blood vessels for drug delivery.

## Contribution

A novel method to engineer nanoparticles with defined membrane proteins for improved targeting and reproducibility.

## Key findings

- PNPs with leukocyte adhesion proteins show enhanced endothelial interactions in a microfluidic model.
- Adhesion-enriched PNPs outperform conventional Leukosomes in accumulating at inflamed endothelium under flow.
- The platform offers better targeting efficiency and translational potential for inflammation-targeted therapies.

## Abstract

Nanoparticles offer a promising strategy for targeted drug delivery while reducing off‐target toxicity. Biomimetic nanoparticles, which integrate native cell components, enhance biological compatibility but often suffer from poorly defined protein compositions that hinder reproducibility and clinical translation. Here, we present a next‐generation biomimetic approach to engineer Particular Nanoparticles (PNPs)‐ formulation enriched with specific, functionally relevant membrane proteins for precise control and tunability. We incorporated leukocyte adhesion proteins (including CD18, CD11a, and CD11b) into the nanoparticle membrane to enhance targeting of inflamed sites. Using a 2D microfluidic model that mimics human blood vessels, adhesion‐enriched PNPs demonstrated significantly improved endothelial interactions and greater accumulation under flow at inflamed endothelium compared to conventional Leukosomes. This protein‐defined biomimetic nanoparticle platform offers enhanced targeting efficiency, improved reproducibility, and translational potential for inflammation‐targeted therapies.

Particular nanoparticles (PNPs), engineered with defined enrichment of leukocyte adhesion membrane proteins, demonstrate superior targeting of inflamed sites in a microfluidic inflamed vessel model under flow conditions. This selective membrane protein enrichment enhances targeting efficiency while improving nanoparticle production reproducibility and translational potential for inflammation‐targeted drug delivery.