Targeting extracellular vesicle delivery to the lungs by microgel encapsulation

Area of Science:

• Biomedical Engineering
• Regenerative Medicine
• Nanotechnology

Background:

• Extracellular vesicles (EVs) from stem cells show therapeutic promise but face rapid clearance challenges.
• Targeting EVs to specific organs, like the lungs, is difficult due to rapid systemic clearance, primarily by the liver.
• Microencapsulation in hydrogels can improve cell survival and engraftment, suggesting potential for EV delivery.

Purpose of the Study:

• To encapsulate mesenchymal stromal cell (MSC)-derived EVs within microgels for targeted lung delivery.
• To investigate the biodistribution and lung retention of microgel-encapsulated EVs after systemic administration.
• To evaluate the cellular uptake of microgel-encapsulated EVs by lung cells, particularly immune cells.

Main Methods:

• Mesenchymal stromal cell (MSC)-derived EVs were labeled with a lipophilic dye (DiR) and encapsulated in agarose-gelatin microgels.
• In vitro uptake studies were performed using endothelial cells and bone marrow-derived macrophages.
• Biodistribution and lung retention were assessed in vivo following intrajugular administration, with cellular uptake analyzed by flow cytometry.

Main Results:

• Microgel-encapsulated EVs were selectively retained in the lungs for up to 72 hours, unlike free EVs cleared by the liver.
• Lung cells, especially CD45+ immune cells, showed greater uptake of microgel-encapsulated EVs compared to free EVs.
• In vitro studies indicated that encapsulated EVs were taken up by endothelial cells and macrophages, though less efficiently than free EVs.

Conclusions:

• Microencapsulation of EVs within microgels is a viable strategy for targeted lung delivery and retention.
• This approach enhances EV accumulation and uptake within lung tissues, particularly by immune cells.
• Microencapsulation offers a novel tool to improve the therapeutic efficacy of cell-free EV delivery systems.