# Macrophage-biomimetic nanomedicine for targeted therapy of abdominal aortic aneurysm via Nrf2/NF-κB pathway

## TL;DR

This paper introduces a new nanomedicine inspired by macrophages to treat abdominal aortic aneurysms by targeting a specific biological pathway.

## Contribution

A macrophage-biomimetic nanomedicine is developed for targeted AAA therapy via the Nrf2/NF-κB pathway.

## Key findings

- MPB-RLZ@MM NPs reduced ROS levels in HUVECs and apoptosis in VSMCs.
- MPB-RLZ@MM NPs inhibited M1-like macrophage polarization via the Nrf2/NF-κB pathway.
- MPB-RLZ@MM NPs delayed aneurysm dilation in vivo after 4 weeks of treatment.

## Abstract

Rationale: Abdominal aortic aneurysm (AAA) is a significant cause of death worldwide, with both mortality and incidence rates gradually increasing. Its complex pathological mechanisms hinder drug development. This work aims to develop a biomimetic multifunctional nanoparticle for targeted AAA therapy.

Methods: Leveraging the multi-pore property of mesoporous Prussian blue nanoparticles (MPB NPs), we encapsulated the rosiglitazone (RLZ) into MPB NPs to synthesize MPB-RLZ NPs. Then, macrophage-biomimetic nanoparticles (MPB-RLZ@MM NPs) were prepared by coating MPB-RLZ NPs with macrophage membranes (MM). The characterization and reactive oxygen species (ROS)-scavenging ability of MPB-RLZ@MM NPs were evaluated. Next, the biocompatibility and biological functions of MPB-RLZ@MM NPs were evaluated. Finally, we assessed the targeting efficacy and therapeutic efficacy of MPB-RLZ@MM NPs in vivo.

Results: MPB-RLZ@MM NPs reduced ROS levels in human umbilical vein endothelial cells (HUVECs) and apoptosis in vascular smooth muscle cells (VSMCs). MPB-RLZ@MM NPs inhibited M1-like macrophage polarization via the Nrf2/NF-κB pathway. In addition, MPB-RLZ@MM NPs accumulated in dilated aneurysms. After 4 weeks of treatment, MPB-RLZ@MM NPs effectively delayed aneurysm dilation.

Conclusions: MPB-RLZ@MM NPs exhibited excellent biosafety and therapeutic efficacy against AAA. This macrophage-biomimetic strategy presents a promising therapeutic approach for AAA treatment.