Gene

microRNA

Extracellular vesicle

Cell biology

Extracellular vesicles

Nanoparticle

Biology

Materials science

Microvesicles

Polymersome

Lipopolysaccharide

Biochemistry

Drug

Immunology

Drug delivery

Polymer

Nanotechnology

Amphiphile

Nanomedicine

Copolymer

Exosome

Inflammation

Pharmacology

Composite material

Chemistry

Biomaterials

Extracellular vesicles (EVs) are nanoscale membrane-formed compartments naturally secreted from cells, which are intercellular mediators regulating physiology and pathogenesis, therefore they could be a novel therapeutic carrier for targeted delivery. However, the translation of EVs is hindered by the heterogeneous composition, low yield, inefficient drug loading and unlikely scalability. Here we report a strategy to generate EVs using nitrogen cavitation (NC-EVs) that instantly disrupts neutrophils to form nanosized membrane vesicles. NC-EVs are similar to naturally secreted EVs (NS-EVs), but contain less subcellular organelles and nuclear acids. The production of NC-EVs was increased by 16 folds and is easy to scale up for clinical use compared to NS-EVs. To examine the usefulness of NC-EVs as a drug delivery platform, piceatannol (an anti-inflammation drug) was remotely loaded in NC-EVs via the pH gradient. We found that piceatannol-loaded NC-EVs dramatically alleviated acute lung inflammation/injury and sepsis induced by lipopolysaccharide (LPS). Our studies reveal that nitrogen cavitation is a novel approach to efficiently generate EVs from any cell type and could be exploited for personalized nanomedicine.

High yield, scalable and remotely drug-loaded neutrophil-derived extracellular vesicles (EVs) for anti-inflammation therapy