Novel production process for therapeutic nanovesicles


May 24, 2023

(Nanowerk News) Particles known as extracellular vesicles play an important role in communication between cells and in many cell functions. Released by the cell into its environment, these “membrane particles” comprise the cell membrane that carry a payload of specific signaling molecules, proteins, nucleic acids, and lipids. Unfortunately, only a small number of vesicles are spontaneously formed by the cell.

Extracellular vesicles for medical applications

The contents of these extracellular vesicles vary depending on the origin and condition of the cell, as do the proteins anchored to the surface of the vesicles. Researchers use these properties to develop new techniques for diagnosing cancer, for example, based on the analysis of extracellular vesicles isolated from blood samples.

Extracellular vesicles may also play a key role in the development of next-generation therapies. Because vesicles come from nature, they are biocompatible and can trigger many different reactions in the body.

Therefore, researchers hope to use the particles to influence the immune system – for example, to destroy cancer cells. To date, however, one major challenge has been the reproducible production of the large number of homogeneous vesicles required for such studies. extracellular vesicles (red) produced using a new technique absorbed in vitro by immune cells (green; nuclei are turquoise) Extracellular vesicles (red) produced using the new technique are absorbed in vitro by immune cells (green; nuclei are turquoise) and can therefore affect the immune response of the organism. (Image: C. Alter, Department of Pharmaceutical Sciences, University of Basel)

Faster route to more particles

Now, a research team led by Professor Jörg Huwyler from the Department of Pharmaceutical Sciences and the Swiss Nanoscience Institute (SNI) from the University of Basel have developed a highly efficient preparation method for extracellular vesicles that generates up to 100 times more particles per cell. and hours than conventional methods. They describe the new method in the journal Communication Biology (“Preparation of high efficiency monodisperse plasma membranes derived from extracellular vesicles for therapeutic applications”).

“We start the preparation process by growing cancer cells, where we induce cell death by adding a chemical stressor,” explained Claudio Alter, first author of the study and doctoral student at SNI PhD School. “The cells then form vesicles, which detach from the host cell after a few hours.”

With a diameter of 1 to 3 micrometers, these giant plasma membrane vesicles are too large for therapeutic applications. In a newly developed process, they are pressed through a filter membrane several times to reduce their size. “After passing through several filters, we obtained a homogeneous solution of nano plasma membrane vesicles (nPMV) with a diameter of 120 nanometers – exactly what we needed for our next application,” explains Alter.

Different origin, different application

The research team then characterized these nPMVs and compared their size, homogeneity, and protein and lipid loading with those of exosomes – currently the most commonly used extracellular vesicles. They also investigated how well nPMV interacted with other cells. In this analysis, the nano plasma membrane vesicles exhibit similar properties to exosomes.

“Their special card and the presence of a membrane-bound marker derived from stem cell lines offers the possibility to use nPMV for therapeutic purposes,” said Jörg Huwyler. “Right now, we are mainly thinking about stimulation of the immune system – for example, in vaccinations or immunotherapy treatments for cancer.”


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