Macrophage-Targeted GSH-Depleting Nanocomplexes for Synergistic Chemodynamic Therapy/Gas Therapy/Immunotherapy of Intracellular Bacterial Infection

Abstract

Intracellular pathogens can survive inside the macrophages to protect themselves from eradication by the innate immune system and conventional antibiotics, resulting in severe bacterial infections. In this work, an antibiotic-free nanocomplex (HA/GA-Fe@NO-DON), exhibiting macrophage-targeted synergistic gas therapy (nitric oxide, NO)/chemodynamic therapy/immunotherapy, was reported. HA/GA-Fe nanoparticles were synthesized by the strong coordination interactions among carboxyl groups of hyaluronic acid (HA), polyphenol groups of gallic acid (GA), and Fe(II) ions. The hydrophobic glutathione (GSH)-responsive NO donor (NO−DON) was encapsulated in HA/GA-Fe nanoparticles to form the final nanocomplexes (HA