Hybrid biomineralized nanovesicles to enhance inflamed lung biodistribution and reduce side effect of glucocorticoid for ARDS therapy.

Acute respiratory distress syndrome (ARDS) is a critical illness characterized by severe lung inflammation. Improving the delivery efficiency and achieving the controlled release of anti-inflammatory drugs at the lung inflammatory site are major challenges in ARDS therapy. Taking advantage of the increased pulmonary vascular permeability and a slightly acidic-inflammatory microenvironment, pH-responsive mineralized nanoparticles based on dexamethasone sodium phosphate (DSP) and Ca2+ were constructed. By further biomimetic modification with M2 macrophage membranes, hybrid mineralized nanovesicles (MM@LCaP) were designed to possess immunomodulatory ability from the membranes and preserve the pH-sensitivity from core nanoparticles for responsive drug release under acidic inflammatory conditions. Compared with healthy mice, the lung/liver accumulation of MM@LCaP in inflammatory mice was increased by around 5.5 times at 48 h after intravenous injection. MM@LCaP promoted the polarization of anti-inflammatory macrophages, calmed inflammatory cytokines, and exhibited a comprehensive therapeutic outcome. Moreover, MM@LCaP improved the safety profile of glucocorticoids. Taken together, the hybrid mineralized nanovesicles-based drug delivery strategy may offer promising ideas for enhancing the efficacy and reducing the toxicity of clinical drugs. Hybrid mineralized nanovesicles improved the drug delivery efficiency to the lungs, suppressed the inflammatory conditions effectively, and meanwhile reduced side effects of glucocorticoids. [Display omitted] • Dexamethasone-based mineralized nanoparticles achieved pH-responsive drug release behavior. • Biomimetic modification enhanced immunomodulatory ability. • Hybrid mineralized nanovesicles increased lung accumulation based on ELVIS effect and improved the safety profile of glucocorticoids. [ABSTRACT FROM AUTHOR]