The carriers are engineered versions of extracellular vesicles, nanoscale membrane-bound particles naturally released by cells to transport molecular signals. Because they resemble biological structures, naturally occurring extracellular vesicles have attracted interest as potential vehicles for therapeutic cargo. However, their production can be difficult to scale, and their ability to carry different types and quantities of therapeutic material is often limited. The Ohio State researchers sought to preserve the biological compatibility of red-blood-cell-derived vesicles while gaining greater control over their size, composition and payload.

The team began with expired red blood cells obtained from the laboratory of Andre Palmer, a professor of chemical and biomolecular engineering at Ohio State. These cells can no longer be transfused into patients, but their membranes remain a source of valuable lipids. Palmer’s laboratory already uses hemoglobin recovered from expired blood to develop red blood cell substitutes. In the new platform, the researchers repurposed the remaining cellular material to produce vesicle membranes. Using discarded blood as a starting material could make the approach more sustainable while providing lipids that are naturally adapted to interacting with the bloodstream.

The particles were assembled with microfluidic technology, a method that manipulates very small volumes of fluid through precisely designed channels. As the red-blood-cell lipids pass through the microfluidic system, they organize into nanoscale vesicles around selected therapeutic materials. This approach allows cargo to be incorporated during vesicle formation rather than added in a separate loading step. The distinction is important because post-production loading can damage fragile molecules, reduce the amount of cargo that enters the carrier or create batch-to-batch variation. Microfluidic assembly also gives researchers more control over the resulting vesicles and expands the range of materials they can encapsulate.

In laboratory experiments, the engineered vesicles were capable of carrying genetic material and proteins, as well as adeno-associated viruses, or AAVs. AAVs are widely used as delivery vehicles in gene therapy because they can transport therapeutic genetic instructions into cells. Their usefulness, however, can be limited by the immune system. Some patients have pre-existing antibodies against AAVs, while others may develop immune responses after treatment. The Ohio State team tested whether placing AAV particles inside the red-blood-cell-derived vesicles would preserve their gene-delivery activity while providing an additional protective layer.

The researchers reported that encapsulated AAV remained functional and could still deliver genetic material into cells. They also found evidence that the vesicles shielded the viral vectors from neutralizing antibodies. This result suggests that the particles might eventually help address one of the central problems in viral gene therapy: the immune system can recognize the viral shell before the vector reaches its intended target. The findings do not establish safety or therapeutic effectiveness in humans, but they demonstrate that the vesicles can act as an additional physical barrier without preventing the virus from performing its gene-delivery role.

The team also engineered the vesicle surface to influence how the immune system and diseased cells responded to the particles. Attaching a peptide derived from CD47 to the outer membrane was intended to produce a “self” signal. CD47 is a molecule associated with protection from engulfment by macrophages, immune cells that identify and remove foreign or damaged material. Experiments indicated that CD47-decorated vesicles were less likely to be mistaken for pathogens and consumed by macrophages. Avoiding this rapid clearance could extend the time that therapeutic carriers remain in circulation and increase the opportunity for them to reach tissues beyond the bloodstream.

A second modification gave the vesicles a more selective interaction with tumors. The researchers added molecules that recognize PD-L1, an immune-regulatory protein found on the surface of many cancer cells, including breast tumors that express the target. The anti-PD-L1 nanobodies used in the study were developed in the laboratory of Ohio State collaborator Blaise Kimmel. In mouse experiments, vesicles carrying the PD-L1-recognition molecules showed preferential uptake in PD-L1-positive breast cancer tumors compared with non-targeted particles. The strategy resembles the targeting logic of cancer immunotherapies, but instead of directing a patient’s T cells to attack a tumor, it could direct therapeutic cargo toward malignant cells.

Animal studies provided an initial picture of how the carriers behave after administration. The engineered vesicles circulated through the mice and distributed to several organs in patterns broadly similar to those reported for naturally occurring extracellular vesicles. The lungs showed particularly notable accumulation, a feature that may guide the next phase of development. The researchers plan to investigate the platform for gene therapy and other treatments that could benefit from delivery to pulmonary tissue. Further work will be required to determine how long the vesicles persist, how their materials are metabolized, whether repeated dosing is possible and whether their targeting performance translates from mice to humans.

The study presents the red-blood-cell-derived vesicles as a flexible biological delivery system rather than as a finished therapy. Their membrane composition closely resembles that of natural red-blood-cell extracellular vesicles, which may help explain their compatibility with the body. At the same time, microfluidic production allows investigators to define the cargo and add functional molecules to the surface with greater precision. By combining a source of otherwise discarded blood material with programmable nanomanufacturing, the researchers have created a platform that could carry therapeutic molecules of very different sizes. Before clinical use can be considered, the technology will need extensive testing for manufacturing consistency, biodistribution, immune effects, toxicity and therapeutic benefit. For now, the results suggest that engineered red-blood-cell vesicles could provide a new way to protect viral gene therapies, direct treatments toward tumors and exploit the natural circulation patterns of biological nanoparticles.

Subject of Research: Not applicable

Article Title: Microfluidic Nano-Assembly of Red-Blood-Cell (RBC) Lipids and Components for Engineering Extracellular Vesicles

Web References:
https://advanced.onlinelibrary.wiley.com/doi/10.1002/adhm.202504351
https://news.osu.edu/shedding-new-light-on-the-tiny-bubbles-sending-signals-between-cells/
https://news.osu.edu/leaps-in-artificial-blood-research-aim-to-improve-product-safety-efficacy/

References:
Advanced Healthcare Materials. DOI: 10.1002/adhm.202504351

Keywords: extracellular vesicles, red blood cells, nanocarriers, gene therapy, AAV, viral vectors, cancer targeting, CD47, PD-L1, microfluidics, drug delivery, Ohio State University

A team led by researchers at the University of Tokyo reports a strategy to strengthen the “self recognition” behavior of vesicles. Instead of relying on natural surface interactions, they engineered vesicle membranes by decorating them with lanthanide metal ions. This modification creates additional binding interfaces that enhance affinity beyond what cells would typically achieve.

Lanthanides such as europium and terbium form strong associations with sialic acid, a sugar motif abundant on many cancer cell surfaces. By tuning vesicle chemistry to display complementary grip points, the researchers enabled engineered vesicles and matching cells to bind rapidly and selectively, even when vesicles originating from many other cell types are present simultaneously.

The practical outcome is speed and sensitivity. A capture process that previously required more than two days was compressed to roughly three hours, while maintaining high selectivity. In experiments, the enhanced interactions were associated with a large signal boost, supporting detection of extremely low-abundance cancer-related vesicle signals.

To translate the approach beyond cell culture, the team tested their platform in mice and then evaluated it using human triple-negative breast cancer samples. They demonstrated two complementary assay modes: a detector that captures cancer-associated vesicles and a probe vesicle that homes to cancer cells to amplify the readout.

According to the study, the signal amplification can reach on the order of 10,000-fold. With that boost, the method aims to make it feasible to identify even a single cancer cell within complex samples using equipment common to standard laboratory workflows, rather than relying on specialized, high-throughput instrumentation.

Beyond diagnostics, the work suggests a modular design principle for extracellular vesicle engineering. Because the platform modifies vesicles’ surface recognition properties, it could be adapted to improve targeted delivery of therapeutics, investigate cell behavior, or support future biomaterial systems aimed at controlled “cell–vesicle” interactions.

Subject of Research: Cells; extracellular vesicles; cancer detection
Article Title: Super homotypic targeting by surface engineering of extracellular vesicles
News Publication Date: 23-Jul-2026
Web References: https://www.nature.com/articles/s41551-026-01743-2
References: DOI: 10.1038/s41551-026-01743-2; Nature Biomedical Engineering
Image Credits: ©2026 Goda et al. CC-BY-ND

Keywords: extracellular vesicles, lanthanide ions, sialic acid, liquid biopsy, cancer diagnostics, homotypic targeting, signal amplification, Nature Biomedical Engineering, targeted drug delivery