Coated Nanovectors Remain in the Organism for Longer. New Outlooks for Tumour Therapies
Liposomes are one of the most recent breakthroughs in the biomedical field. They are empty microspheres formed by one or more double layers of lipids that are used to deliver drugs for antitumor therapies. Their use provides a series of advantages of traditional technology such as the possibility of reducing drug dosage to increase their therapeutic efficiency or transporting a drug to a specific organ, avoiding potentially damaging side effects. However, notwithstanding these enormous advantages, only a few types of liposomes are stably used in clinical practice.
The international research team, coordinated by Prof. Giulio Caracciolo in collaboration with Alessandra Zingoni and Isabella Screpanti from the Department of Molecular Medicine, have established that the limited clinical success of liposomes is mainly due to the changes they undergo when they come into contact with blood. Once injected into the organic liquid, these lipidic vesicles are coated by plasmatic proteins that form a protein layer. In fact, the scientific erroneously believed for decades that it was the surface of the liposome that interacted with the biological systems of the organism, whereas it really is the protein layer that plays a central role in regulating activity inside of cells. What the immune system fights is not the liposome itself, but its protein coating.
This observation led the researchers to identify a procedure for tricking the immune system into “accepting” nanovectors transporting pharmacological therapies.
“Coating liposomes with an artificial protein layer of human plasma,” explains Giulio Caracciolo, “allows us to drastically reduce the uptake by leukocytes and to prolong the circulation of the lipidic vesicles in the organism, thereby increasing their therapeutic efficiency.”
This discovery will have numerous applications, but the most relevant is certainly for tumour immunotherapy, as well as uses in other biomedical areas.
The study, conducted in collaboration with researchers from Michigan State University, the University of Technology of Graz in Austria and the Centre for Life Nano Science at the Italian Institute of Technology, has published on Nature Communications.
Interplay of protein corona and immune cells controls blood residency of liposomes - Giulimondi F., Digiacomo L., Pozzi D., Palchetti S., Vulpis E., Capriotti A.L., Zenezini Chiozzi R., Laganà A., Amenitsch H., Masuelli L, Mahmoudi M., Screpanti I., Zingoni A., Caracciolo G. Nature Communications (2019, 10:3686) DOI https://doi.org/10.1038/s41467-019-11642-7
Giulio Caracciolo, Department of Molecular Medicine
Alessandra Zingoni, Department of Molecular Medicine