Developing Biomaterial-Based mRNA Delivery System for Lung Disease Treatment.

Lung disease remains a persistent global health challenge. Advances in medical research have led to innovative strategies to combat these conditions, with biomaterials emerging as a promising platform for targeted drug delivery. Various biomaterials-including nanoparticles such as liposomes, polymers, hybrid systems, dendritic polymers, gold nanoparticles, mesoporous silica, calcium carbonate, and exosomes-exhibit excellent biocompatibility. These materials protect therapeutic agents from nuclease degradation, stabilize drug carriers, and enhance cellular uptake via mechanisms such as endocytosis. Chemical modifications further improve biomaterials by facilitating endosomal escape and conjugation with targeting ligands, thereby enabling precise delivery to specific cells or tissues. As a therapeutic modality, mRNA offers high biosafety, notable controllability, efficient translation, and immunomodulatory properties. This review evaluates the impact of lung structure on drug absorption, examines delivery mechanisms associated with various biomaterial types, and presents application examples. It also summarizes recent research developments, discusses clinical limitations, and explores future research directions for biomaterials in lung disease therapy. Additionally, it highlights the role of biomaterials in stabilizing and protecting mRNA, providing insights into the advancement of mRNA-based therapeutics. This review aims to establish a robust theoretical foundation and offer practical guidance for biomaterial-based mRNA therapies in treating lung diseases.