Researchers at The Ohio State University have developed a configurable nanocarrier system using lipids from expired human red blood cells. As detailed in a study published in Advanced Healthcare Materials, the microfluidic-assembled vesicles successfully encapsulated genetic cargo, proteins, and viral vectors while evading immune clearance and targeting cancer cells in laboratory tests.
Sustainable Lipids From Expired Blood Supplies
Modern nanomedicine continually runs into biological hurdles when trying to shepherd therapeutic payloads through the human body. Natural extracellular vesicles—tiny nanoscale membrane structures naturally released by cells to shuttle molecular signals—offer inherent biocompatibility. Yet scaling up their production while maintaining cargo-loading flexibility has historically frustrated researchers. A team at The Ohio State University bypassed these biological limitations by assembling the vesicles from red blood cell lipids using microfluidics, creating a highly controllable manufacturing platform.
The source material for these carriers originates directly from medical waste streams. Expired red blood cells, which can no longer be transfused into patients and would otherwise face disposal, are supplied by the laboratory of Andre Palmer, a chemical and biomolecular engineering professor and Ohio Eminent Scholar at the university. Palmer’s lab routinely purifies hemoglobin from expired units to develop blood 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.”
Andre Palmer, professor of chemical and biomolecular engineering, Ohio State
Microfluidic Assembly and Precise Cargo Integration
By shifting from natural cell harvesting to engineered microfluidics, the researchers gained precise oversight over the structural composition of the resulting vesicles. Traditional manufacturing often requires producing empty vesicles first and forcing therapeutic cargo inside afterward—a post-production loading step that can damage fragile molecules and create inconsistent batches.
Microfluidic technology manages very small volumes of fluid through precisely channeled pathways. As red blood cell lipids travel through these channels, they automatically organize into nanoscale vesicles around the chosen therapeutic material. This simultaneous encapsulation method permits the incorporation of large, delicate biological components during the actual formation of the vesicle.
The resulting particles closely match the lipid composition of natural red blood cell extracellular vesicles. This preservation of native biochemical properties ensures that the synthetic carriers remain highly biocompatible while granting researchers command over size and payload volume.
Evading Immune Detection and Targeting Tumors
Unmodified foreign particles entering the bloodstream are quickly intercepted and consumed by macrophages—the immune system’s frontline defensive scavengers. To prevent this premature clearance, the Ohio State team modified the outer surface of their engineered carriers.
Beyond simple immune evasion, the carriers can be programmed to home in on diseased tissue.
Shielding Viral Vectors in Gene Therapy Delivery
Gene therapy relies heavily on adeno-associated viruses, or AAVs, to transport corrective genetic instructions into human cells.
To overcome this barrier, the Ohio State team encapsulated intact AAV particles directly inside the engineered red blood cell vesicles. Testing revealed that the encasement did not impede the virus’s core function.
“Our thought was to take these AAV particles and encapsulate them inside engineered RBC extracellular vesicles. We tested if the gene therapy would still work and be delivered into cells, and we show that it would. And we also demonstrated that the AAVs would be protected from neutralizing antibodies.”
Eduardo Reátegui, professor of chemical and biomolecular engineering, Ohio State
Future Directions and Pulmonary Applications
When evaluated in animal models, the engineered nanocarriers remained in active circulation and distributed across multiple organ systems in distribution patterns mirroring natural extracellular vesicles. Researchers observed a notable accumulation of the particles within pulmonary tissue.
