Engineered Blood Cell Vesicles Show Promise as Drug Delivery Vehicles

Red blood cells are serving as the foundation for nanocarriers that a new study suggests could work as effective and efficient vehicles for gene therapy, tumor targeting, and other medical treatments. Scientists at The Ohio State University showed that engineered extracellular vesicles could evade immune cells and target cancer cells, two capabilities that could improve the delivery of future therapies.

The vesicles are assembled from red blood cell lipids using microfluidics, allowing researchers to package cargo ranging from genetic material and proteins to whole viruses used in gene therapy. In mice, the engineered vesicles remained in circulation and distributed to multiple organs in patterns similar to naturally occurring extracellular vesicles, with notable accumulation in the lungs. 

The team originally set out to build delivery devices from natural extracellular vesicles generated by red blood cells but ran into limitations scaling up production and cargo-loading flexibility, prompting them to turn to engineering techniques. “In terms of lipid composition, they basically match very closely with what the natural extracellular vesicles from red blood cells would have,” said Eduardo Reátegui, senior author of the study published in Advanced Healthcare Materials. “We are keeping some of the great biological advantages that these particles have by themselves because they are very biocompatible.”

The lipids come from expired red blood cells obtained from the lab of co-author Andre Palmer, whose lab purifies hemoglobin from expired blood as a building block for red blood cell substitutes. “The approach here is very sustainable because these expired red blood cells otherwise would be thrown out since they cannot be transfused into patients,” Palmer explained.

The microfluidics process allows therapeutic cargo to be incorporated as the vesicles form, removing the need for separate loading steps. Attaching a CD47 peptide to the carriers’ surface protected them from being mistaken for pathogens and consumed by macrophages, while adding PD-L1-recognition molecules, including anti-PD-L1 nanobodies developed in co-author Blaise Kimmel’s lab, enabled preferential uptake in PD-L1-positive breast cancer tumors. Researchers said these engineered vesicles could function similarly to CAR T-cell therapies made from a patient’s own immune cells. 

The method also allowed inclusion of larger molecules, including an adeno-associated virus (AAV), a common gene therapy delivery vehicle. Reátegui said encasing a therapeutic AAV inside a CD47-tagged vesicle could reduce the chance of triggering an immune response, and testing showed the gene therapy still worked while the AAV was shielded from neutralizing antibodies. The researchers now plan to focus on gene therapy applications, particularly those that take advantage of the vesicles’ affinity for the lungs.