This article has been reviewed according to Science X's editorial process and policies. Editors have highlighted the following attributes while ensuring the content's credibility: Red blood cells serve as the foundation for nanocarriers that show promise in a new study as effective and efficient vehicles for gene therapy, tumor targeting and other medical treatments. Scientists at The Ohio State University have showed that the engineered extracellular vesicles could evade immune cells and target cancer cells, two capabilities that could improve the delivery of future therapies.
The study is published in Advanced Healthcare Materials. The technology offers exceptional flexibility: By assembling the vesicles from red blood cell lipids using microfluidics, researchers were able 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 were distributed to multiple organs in patterns similar to those of naturally occurring extracellular vesicles, with notable accumulation in the lungs.
Though researchers started with the idea of making delivery devices out of natural extracellular vesicles generated by red blood cells, they encountered limitations in efforts to scale up production and cargo-loading flexibility—so they turned to engineering techniques to improve upon what nature had to offer. "In terms of lipid composition, they basically match very closely with what the natural extracellular vesicles from red blood cells would have," said senior author Eduardo Reátegui, professor of chemical and biomolecular engineering at Ohio State. "We are keeping some of the great biological advantages that these particles have by themselves because they are very biocompatible." The source cells for the lipids are expired red blood cells—or RBCs—obtained from the lab of co-author Andre Palmer, professor of chemical and biomolecular engineering and an Ohio Eminent Scholar at Ohio State.
"We're always purifying hemoglobin from expired red blood cells," said Palmer, whose lab uses the hemoglobin as a building block for making red blood cell substitutes. "The approach here is very sustainable because these expired red blood cells would otherwise be thrown out since they cannot be transfused into patients." Extracellular vesicles (EVs) are tiny cargo-containing particles that emerge from cells to transport signals to other cells. EVs are known to contribute to both health and disease, and the Ohio State team has been investigating how engineered EVs can be used in a variety of medical applications.
Beyond the biocompatibility provided by red blood cell lipids, microfluidics enables therapeutic cargo to be incorporated as the vesicles form, eliminating the need for separate cargo-loading steps afterward. "We're not saying our process is better. We're claiming that we have a lot more controllability in terms of what we want the composition of this engineered vesicle to look like," said Reátegui, also a member of the Cancer Biology Program in The Ohio State University Comprehensive Cancer Center.
Experiments showed that attaching a CD47 peptide to the carriers' outer surfaces protected them from being mistaken for pathogens and eaten by macrophages. The team also showed that the vesicles could be engineered for tumor targeting by adding PD-L1-recognition molecules, including anti-PD-L1 nanobodies developed in the lab of co-author Blaise Kimmel, and by demonstrating preferential uptake of anti-PD-L1-tagged vesicles in PD-L1-positive breast cancer tumors that are often targeted by immunotherapy. In fact, researchers said these engineered EVs could function similarly to cancer CAR T-cell therapies that are made from a patient's own immune system T cells.
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