Medicines made of solid gold to help the immune system
By studying the effects of gold nanoparticles on immune cells linked to the production of antibodies, researchers from UNIGE, Swansea University and NCCR "Materials of organic inspiration" are paving the way for more effective vaccines and therapies.
In the last twenty years, the use of nanoparticles in medicine has steadily increased. However, their safety and effect on the human immune system remains a major concern. By testing a variety of gold nanoparticles, researchers at the University of Geneva (UNIGE), in collaboration with the National Center for Research Expertise "Materials of bio inspiration" and Swansea University Medical School, (United Kingdom), are providing the first evidence of their impact on human B lymphocytes - the immune cells responsible for antibody production. The use of these nanoparticles is expected to improve the effectiveness of pharmaceutical products while limiting potential adverse effects. These results, published in the journal ACS Nano, will lead to the development of more targeted and better tolerated therapies, particularly in the field of oncology. The developed methodology also allows the biocompatibility of any nanoparticle to be tested at an early stage in the development of a new nano-traffic.
B lymphocytes are a crucial part of the human immune system as they are responsible for the production of antibodies, therefore interesting for the development of preventive and therapeutic vaccines. However, to achieve their goal, vaccines need to reach B cells quickly without being destroyed, making the use of nanoparticles particularly useful. "Nanoparticles can be a protective vehicle for vaccines - or other drugs - to transport them specifically where they can be more effective, saving other cells," explains Carole Bourquin, a professor at the UNIGE Faculty of Medicine and Science, which has -guided this study. "This targeting also allows the use of a lower dose of immunostimulant while maintaining an effective immune response. It increases its effectiveness by reducing side effects, provided that the nanoparticles are harmless to all immune cells."
Gold is an ideal material
Gold is an excellent candidate for nanomedicine due to its particular physico-chemical properties. Well tolerated by the body and easily malleable, this metal has, for example, the peculiarity of absorbing light and therefore releasing heat, a property that can be exploited in oncology. "Gold nanoparticles can be used to target tumors. When exposed to a light source, nanoparticles release heat and destroy nearby cancer cells. We could also connect a drug to the surface of nanoparticles to be delivered to a specific location," explains Sandra Hočevar, UNIGE researcher. "To test their safety and the best formula for medical use, we have created gold spheres with or without polymer coating, as well as gold bars to explore the effects of coating and form. We then exposed human B lymphocytes to our particles for 24 hours to examine the activation of the immune response. "
Following the activation markers expressed on the surface of B cells, the scientists were able to determine how their nanoparticles activate or inhibit the immune response. Although none of the nanoparticles tested showed adverse effects, their influence on the immune response differed according to their shape and the presence of a surface, polymer coating. "The surface properties and morphology of nanoparticles are certainly important when it comes to the cell-nanoparticle interaction. It is interesting to note that gold nanorods have inhibited the immune response instead of activating it, probably causing interference on the cell membrane, or because they are heavier, "says Martin Clift, associate professor of nanotoxicology and in vitro systems at Swansea University Medical School, and the co-leader of the project.
Uncoated spherical particles aggregate easily and therefore are not suitable for biomedical use. On the other hand, the gold spheres coated with a protective polymer are stable and do not compromise the functionality of the B lymphocytes. "And we can easily place the vaccine or drug to be delivered to B lymphocytes in this coating," says Carole Bourquin. "Furthermore, our study established a methodology to evaluate the safety of nanoparticles on B lymphocytes, something that had never been done before. "This could be particularly useful for future research, as the use of nanoparticles in medicine still requires clear guidelines."
Many clinical applications
B cells are at the heart of the vaccine response, but also in other areas such as oncology and autoimmune diseases. Gold nanoparticles developed by the research team could allow existing drugs to be supplied directly to B cells to reduce the necessary dosage and potential side effects. In fact, studies have already been conducted on patients for the treatment of brain tumors. Gold nanoparticles can be made small enough to cross the blood-brain barrier, allowing the direct administration of specific anti-tumor drugs in cancer cells.