Engineering nanoparticles for macrophage reprogramming in chronic inflammatory diseases: current advances, challenges, and future perspectives.

Inflammation is essential for host defense and tissue repair, yet its dysregulation contributes to the development of numerous chronic diseases. Macrophages play a central role in these processes through their remarkable functional plasticity and ability to adopt pro-inflammatory or pro-resolving states. Nanoparticles have emerged as promising immunomodulatory platforms capable of reprogramming macrophage function through precisely engineered physicochemical properties. This review examines how nanoparticle characteristics, including size, surface charge, surface functionalization, biomimetic coatings, and microenvironment-responsive features, influence macrophage reprogramming across diverse chronic inflammatory diseases. Comparative analysis reveals that successful nanoplatforms frequently target conserved inflammatory pathways, including NF-κB, NLRP3, HIF-1α, and oxidative stress-associated pathways. We further highlight emerging structure-function relationships, translational challenges, and key design principles that can guide the development of next-generation nanotherapeutics aimed at restoring homeostasis in chronic inflammatory diseases.