Carnegie Mellon University researchers have created an “all-purpose” platform for utilizing exosomes to deliver cargo in living organisms. Their method can be used to develop a new class of hybrid nanoparticles for delivering therapeutics aimed at treating or preventing a variety of diseases, including anti-cancer drugs and immunotherapies for organ transplantation.
Exosomes are a type of extracellular vesicle of nanometer size that can be shed from every cell in our body and can hold a variety of cargo, including proteins, lipids, metabolites and nucleic acids. Although long thought to be cellular waste, exosomes are now known to play a key role in cell communication with other neighboring and distant cells.
In recent years, there has been an explosion in exosome research, with scientists trying to harness these biological nanoparticles for drug delivery. However, most techniques rely on modifying the exosomes in ways that require complex molecular biology tools or degrade the exosome’s innate functionality.
In a paper published in ACSNano, Carnegie Mellon doctoral candidates Sushil Lathwal and Saigopalakrishna “Sai” Yerneni, with an interdisciplinary team of chemists and biomedical engineers from Carnegie Mellon and the University of Louisville, have overcome many of these limitations by creating a method that rapidly and efficiently engineers exosomes with a DNA-cholesterol tether. The team showed that the single stranded synthetic DNA with attached cholesterol could bind with a complementary strand of DNA linked to a bioactive agent. As a result, the researchers were able to connect a number of different types of cargo to the exosome surface, enabling a number of functions. For example, the DNA tether could be used to label an exosome with a dye molecule for imaging studies or to attach an antibody or drug to an exosome for the treatment or prevention of a disease.
“Sushil and Sai have created a versatile platform that will allow us to use exosomes for research and therapeutics in a number of areas,” said Subha R. Das, associate professor of chemistry and member of the Center for Nucleic Acids Science and Technology. “Our system allows us to display an array of molecules on exosome surface.”
This platform can be directly applied to any isolated population of exosomes regardless of the cell, the tissue, or the organism.
Phil Campbell, Research Professor, Engineering Research Accelerator
“This platform can be directly applied to any isolated population of exosomes regardless of the cell, the tissue, or the organism,” said Phil Campbell, research professor of biomedical engineering and member of the Engineering Research Accelerator.
In their study, the researchers showed that their method could be used with exosomes from different biological sources, which could dramatically speed up exosome modification. As a proof-of-concept, they not only demonstrated that the DNA-cholesterol tether could be used to alter how exosomes interacted with cancer cells but also to deliver immune-active cargo for applications in organ/tissue transplantation.
The researchers plan to continue to develop this platform to create new, powerful modifications for exosomes that can be used in a variety of applications.
Study authors include: Lathwal, Das, and Krzysztof Matyjaszewski from the Carnegie Mellon Department of Chemistry; Yerneni and Campbell from the Carnegie Mellon Department of Biomedical Engineering; Lee Weiss from the Carnegie Mellon Department of Biomedical Engineering and Robotics Institute; and Pradeep Shrestha, Haval Shirwan, and Esma Yolcu from the University of Louisville Department of Microbiology and Immunology.
This study was funded by the National Institutes of Health (AI132817-01) and the Dowd Fellowship at Carnegie Mellon University.