Gold nanoparticles: from San Raffaele research the new frontier to identify and eliminate until now invisible bladder tumors

Over half a million new diagnoses of bladder cancer occur each year. This type of cancer is not only the tenth most common in the world, but it is also one of the most difficult to treat due to resistance to therapy and the presence of so-called “residual disease”. Current diagnostic imaging techniques are in fact unable to detect tumors smaller than 1 millimeter, especially when they are flat, making them extremely difficult to remove. Each year, due to these diagnostic and therapeutic limitations, approximately 200,000 patients experience a tumor relapse, forcing them to undertake multiple long and painful treatment paths or, in the worst cases, to have their bladder removed, procedures that cost the global health system approximately 10 billion dollars a year.

A group of researchers coordinated by Dr. Massimo Alfano, group leader of the Extracellular Microenvironment Unit of the Urological Research Institute - URI directed by Professor Andrea Salonia and of the Urology Unit, directed by Professor Francesco Montorsi of the IRCCS Ospedale San Raffaele, started “EDIT” in 2018, a project in which Vita-Salute San Raffaele University, the CNR of Pisa, the University of Bologna, Ascend Technologies of the United Kingdom, FUJIFILM Visualsonics Inc. of Amsterdam and Monash University of Malaysia also participated. The project was supported by the European Union’s HORIZON 2020 research and innovation program and led today to the publication of the study “Gold nanorods-assisted theranostic solution for non-visible residual disease in bladder cancer” in the Proceedings of the National Academy of Sciences (PNAS). Research demonstrates the efficacy and safety in preclinical models of using gold nanoparticles to diagnose and treat bladder tumors smaller than 1 millimeter, promising to minimize “residual disease” and eliminate the problem of therapy resistance.

Researchers have identified and developed a solution to identify and treat bladder tumors smaller than 1 millimeter: these are “gold nanorods,” real gold ingots a few nanometers long that, once infused into the bladder of mouse models through the urethra, thanks to a specific marker, recognize and bind only to tumor cells. Thanks to the use of a pulsed light, the gold nanoparticles emit ultrasound, making the presence of the small tumor visible through ultrasound. It has also been demonstrated that, if instead of pulsed light, the “gold nanorods” are subjected to continuous light, even of the same wavelength, they heat up, managing to burn and permanently eliminate small tumors that were previously invisible and ineliminable.

We have managed to develop a unique solution for the problems that this form of neoplasia entails. In the clinic it is called the theragnostic approach: thanks to the "gold nanorods" we are able to combine diagnosis and therapy in a single process. Furthermore, since the particles are instilled directly into the bladder and since gold is a biocompatible material, there is no risk of side effects in the surrounding non-neoplastic tissues or organs, effects that a pharmacological or immunotherapeutic therapy could not guarantee,

says Dr. Alfano.

The clinical application of this solution, whose feasibility has been demonstrated in the preclinical model, could reduce the frequency of bladder cancer relapses and the number of patients with recurrent tumors. We expect a great positive impact on the quality of life of patients together with a reduction in social health costs,

confirms Dr. Alfano.

For this reason, in September 2023 the progetto PHIRE was born, always coordinated by Dr. Massimo Alfano and funded by the European Union's Horizon Europe program, whose objective is to bring gold nanorods to the market, of which the IRCCS Ospedale San Raffaele shares the patent with the University of Bologna, for the identification and treatment of bladder tumor lesions smaller than 1 millimeter.

Our research and development project, of which this study presents excellent results, is now looking for industrial and/or financial partners to see this new technology realized and applied, which, we are sure, will be able to make a difference and guarantee the well-being of many patients,

continues Dr. Alfano. San Raffaele Hospital, a pioneer in the field of medical research, is thus pursuing its translational mission, that is, transforming the most promising research results into tangible treatments for patients.

The revolutionary potential of this innovative technology could change the treatment guidelines for bladder cancer. We are confident that the solution identified for residual disease in bladder cancer can also be applied to other forms of neoplasia. The tumor marker recognized by our gold nanorods is also expressed by ovarian and cervical tumors,

concludes Professor Andrea Salonia.