Liposomes are the ideal tool for drug delivery in cancer therapies in the biomedical field. These nanoparticles, made up of one or more lipid bilayers, offer numerous advantages over traditional technologies, such as the possibility of reducing drug doses, increasing selectivity towards target organs and reducing potentially harmful side effects. However, only a small number of liposomal formulations have been approved by regulatory agencies and have entered clinical practice on a permanent basis.

Decades of research have established that the limited clinical success of liposomes is mainly due to the changes they undergo as soon as they come into contact with blood: once introduced into the body fluid, they become covered with a 'protein crown' and are recognised by the immune system as a foreign body to be eliminated. Therefore, what the immune system is fighting is not the liposome itself but the very protein coat it is wearing in the blood.

That is why an international research team, coordinated by Giulio Caracciolo and Saula Checquolo of Sapienza University of Rome, created a protein coating that is invisible to the immune system in order to 'trick' it into accepting the nanoparticles containing the drug therapy.

The biomimetic particle developed by the researchers in a study published in the journal ACS Nano, with the collaboration of the University of Technology of Graz in Austria and Utrecht University in the Netherlands, is called proteoDNAsome. It consists of three distinct compartments: lipids, DNA and proteins.

The innermost layer consists of a lipid core encapsulating the drug to be delivered, which is covered by a DNA coating with a dual purpose: functional and structural. Functionally, DNA is used to express a therapeutically useful protein in the target cell, while its negative electrical charge enables a third and final layer of specific plasma proteins to be adsorbed. This protein layer makes the proteoDNAsome invisible to the immune system.

"Coating the nanoparticles with an artificial protein crown made of human plasma proteins," says Giulio Caracciolo of the Department of Molecular Medicine of Sapienza University, "can drastically reduce uptake by leukocytes and prolong the circulation of lipid vesicles in the body, thus increasing the therapeutic efficacy of drug treatment."

This discovery has numerous applications, most notably in cancer immunotherapy and other biomedical fields.

References:

Opsonin-deficient nucleoproteic corona endows unPEGylated liposomes with stealth properties in vivo - Francesca Giulimondi, Elisabetta Vulpis, Luca Digiacomo, Maria Valeria Giuli, Angelica Mancusi, Anna Laura Capriotti, Aldo Laganà, Andrea Cerrato, Riccardo Zenezini Chiozzi, Carmine Nicoletti, Heinz Amenitsch, Francesco Cardarelli, Laura Masuelli, Roberto Bei, Isabella Screpanti, Daniela Pozzi, Alessandra Zingoni, Saula Checquolo, Giulio Caracciolo - ACS Nano 2022 https://doi.org/10.1021/acsnano.1c07687

Further Information

Giulio Caracciolo
Department of Molecular Medicine
giulio.caracciolo@uniroma1.it

Saula Checquolo
Department of Medico-Surgical Sciences and Biotechnologies
saula.checquolo@uniroma1.it