Genoa (Italy), 20 November 2025 – A patented RNA-based cocktail developed at the Italian Institute of Technology (IIT-Istituto Italiano di Tecnologia) has emerged as a promising active agent against tumors of the central nervous system, such as glioblastoma. The study, published today in the scientific journal Molecular Therapy – Nucleic Acids, demonstrates the effectiveness of a combination of 11 different non-coding RNAs, known as microRNAs (miRNAs), in slowing the growth of cancer cells and enhancing the activity of chemotherapeutic drugs. Tests were carried out on patient-derived cells and on preclinical models. Further validation steps will be required for medical use of the compound.
The protocol was developed by the Neurobiology of microRNA Laboratory of IIT, coordinated by Principal Investigator Davide De Pietri Tonelli. The study also involved researchers from IIT's Nanotechnology for Precision Medicine Laboratory, led by Paolo Decuzzi, the IIT Analytical Chemistry Laboratory, the University of Genoa and the IRCCS Policlinico San Martino. The experimental work was supported by grants from Fondazione AIRC for Cancer Research, coordinated by De Pietri Tonelli.
Glioblastoma is one of the most aggressive brain tumors, and IIT's researchers have identified a new miRNA-based therapeutic strategy capable of slowing its progression and making it more responsive to anticancer drugs such as temozolomide. The same strategy could potentially be applied to other tumor types, as it targets biological mechanisms of adhesion and invasion shared across different kinds of cancer cells.
"Internationally, many clinical trials are testing RNA-based therapeutics, which usually rely on a single RNA molecule that tumors can eventually find ways to evade" explains Davide De Pietri Tonelli, coordinator of the IIT MicroRNA Neurobiology Laboratory. "By using a cocktail of miRNAs, this possibility is reduced, because each miRNA acts on multiple fronts, giving tumor cells far less opportunities to resume their growth."
The research team focused on miRNAs, a type of non-coding RNA involved in gene regulation and in the key biological mechanisms that govern cell behavior, stimulating or inhibiting their growth. In particular, the researchers studied miRNAs involved in the differentiation of stem cells into neurons—a process known as neurogenesis, which generates and maintains healthy cells in the central nervous system, and through this work they identified 11 distinct miRNA molecules.
When a tumor is present, the molecular mechanisms controlled by these miRNAs become altered. Cancer cells proliferate through two main strategies: by lowering the levels of controls, such as miRNAs that would inhibit their growth, and by seeking nutrients and energy from blood vessels to support their division and expansion.
The team demonstrated that introducing that combination of 11 miRNAs into the tumor slows the growth and invasiveness of glioblastoma cells. Tests were performed on tumor cells extracted from patients and on preclinical models.
"Through our genetic and computational studies, we found that these miRNAs work together to slow-down tumor growth, by blocking specific interactions between cancer cells and the environment around them," says Silvia Rancati, first author of the study, a PhD student in Tonelli's group at the time and now a postdoctoral researcher in IIT's Polymers and Biomaterials Laboratory in Genoa.
The miRNA combination was delivered using nanoparticles, like those used in RNA vaccines, although delivery methods could vary depending on the type of anticancer therapy required. The patented formulation has proved effective in the laboratory and will now need to undergo a validation process before reaching clinical application.
"This research highlights the importance of curiosity-driven science and the strength of multidisciplinary collaboration; we brought together neurobiology, nanotechnology, analytical chemistry and computational biology – present at IIT, alongside the clinical expertise available throughout the Ligurian ecosystem," concludes De Pietri Tonelli.
