Gold Nanoparticles: San Raffaele's Research Opens New Frontiers in Detecting and Eliminating Previously Invisible Bladder Tumors

Every year, over half a million new cases of bladder cancer are diagnosed. This type of cancer is not only the tenth most common worldwide but is also one of the most difficult to treat: on the one hand, due to resistance to therapy, and on the other, because of the so-called "residual disease." Current imaging techniques are 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, around 200,000 patients experience a tumor recurrence and are forced to undergo multiple long and painful therapeutic paths or, in the worst cases, bladder removal, procedures that cost global healthcare systems about $10 billion annually.

A group of researchers coordinated by Dr. Massimo Alfano, group leader of the Extracellular Microenvironment Unit at the Urological Research Institute (URI), directed by Professor Andrea Salonia, and the Urology Unit, directed by Professor Francesco Montorsi at Ospedale San Raffaele, launched in 2018 the "EDIT" project. The project also involved the Vita-Salute San Raffaele University, the CNR of Pisa, the University of Bologna, Ascend Technologies from the UK, FUJIFILM Visualsonics Inc. of Amsterdam, and Monash University of Malaysia.

The project was supported by the European Union's HORIZON 2020 research and innovation program and has now led to the publication of the study "Gold nanorods-assisted theranostic solution for non-visible residual disease in bladder cancer" in Proceedings of the National Academy of Sciences (PNAS).

The research demonstrates the efficacy and safety of using gold nanoparticles for the diagnosis and treatment of bladder tumors smaller than 1 millimeter in preclinical models, promising to minimize "residual disease" and eliminate the issue of therapy resistance.

Researchers have identified and developed a solution to detect and treat bladder tumors smaller than 1 millimeter: the "gold nanorods," tiny gold bars just a few nanometers long. Once infused into the bladder of murine models through the urethra, thanks to a specific marker, these nanorods recognize and bind only to cancer cells.

By using a pulsed light, the gold nanoparticles emit ultrasound, making the small tumor visible through ultrasound imaging.

It was also demonstrated that if the "gold nanorods" are exposed to continuous light (though of the same wavelength), they heat up and are able to burn and definitively eliminate the small tumors that were previously invisible and untreatable.

"We have managed to develop a unique solution to the challenges posed by this type of cancer. In the clinic, this is known as a theranostic approach: thanks to the 'gold nanorods,' we are able to combine diagnosis and therapy in a single process," says Dr. Alfano. "Moreover, since the particles are directly instilled into the bladder and gold is a biocompatible material, there is no risk of side effects in the surrounding non-cancerous tissues or organs, something that a pharmacological or immunotherapy could not guarantee."

"The clinical application of this solution, whose feasibility has been demonstrated in a preclinical model, could reduce the recurrence frequency of bladder cancer and the number of patients with recurrent tumors," confirms Dr. Alfano. "We anticipate a significant positive impact on patients' quality of life along with a reduction in healthcare and social costs."

In September 2023, the PHIRE project was launched, also coordinated by Dr. Massimo Alfano and funded by the Horizon Europe program of the European Union. Its goal is to bring the "gold nanorods" to market, co-patented by Ospedale San Raffaele and the University of Bologna, for the identification and treatment of bladder cancer lesions smaller than 1 millimeter.

"Our research and development project, whose excellent results are presented in this study, is now seeking industrial and/or financial partners to see this new technology realized and applied. We are confident that it will make a difference and ensure the well-being of countless patients," continues Dr. Alfano.

Ospedale San Raffaele, always a pioneer in the field of medical research, thus continues its translational mission, which is to transform the most promising research results into tangible treatments for patients.

"The revolutionary potential of this innovative technology could change the guidelines for bladder cancer treatment. We are confident that the solution identified for residual 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 cancers," concludes Professor Andrea Salonia.