Engineered extracellular vesicles derived from red blood cell lipids offer a new platform for targeted gene therapy and cancer drug delivery, according to a study published recently in Advanced Healthcare Materials. Researchers at The Ohio State University developed a microfluidics-based manufacturing technique to build versatile nanocarriers from expired blood supplies, addressing traditional scaling and loading limits of natural biological transport systems.
Microfluidic Engineering of Red Blood Cell Vesicles
Scientists sought to overcome the natural barriers of extracellular vesicles—tiny cargo-transporting particles secreted by cells—which are often difficult to produce at scale or load with specific therapeutic materials. According to Eduardo Reátegui, senior author and professor of chemical and biomolecular engineering at Ohio State, the team utilized microfluidics to assemble vesicles directly from red blood cell lipids. This approach matches the lipid composition of natural extracellular vesicles while retaining key biocompatibility benefits. The method incorporates therapeutic cargo during the actual formation of the vesicles, removing the need for separate post-production loading steps, as noted by Reátegui.
Sustainable Sourcing from Expired Blood Supplies
The raw material for the lipid vesicles comes from expired red blood cells obtained from the laboratory of co-author Andre Palmer, an Ohio Eminent Scholar and professor of chemical and biomolecular engineering at Ohio State. Palmer’s laboratory routinely purifies hemoglobin from expired red blood cells to build blood substitutes. Because these units can no longer be transfused into patients, utilizing them for nanocarrier manufacturing provides a sustainable source for medical engineering, according to Palmer.
Evasion of Immune Cells and Tumor Targeting
In animal experiments involving mice, the engineered vesicles remained in circulation and distributed across multiple organs with notable accumulation in the lungs, mirroring the distribution patterns of naturally occurring extracellular vesicles. To prevent macrophages from clearing the carriers, researchers attached a CD47 peptide to the outer surface, protecting the vesicles from being mistaken for pathogens. Furthermore, the research team added PD-L1-recognition molecules—including anti-PD-L1 nanobodies developed by co-author Blaise Kimmel—to direct the vesicles toward specific cancer cells. Experiments demonstrated preferential uptake of these tagged vesicles in PD-L1-positive breast cancer tumors, pointing toward potential applications that function similarly to CAR T-cell therapies.
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