Nanorobots Delivering Localized Therapy Reduce Bladder Tumors by 90%

 

A promising treatment for bladder cancer involving the use of nanoparticles capable of delivering therapeutic agents directly to the tumor reduced the size of bladder tumors in mice by 90%. These nanoparticles, endowed with the ability to self-propel within the body, delivered a single dose of urea-powered nanorobots. The study was published in the journal Nature Nanotechnology.

These tiny nanomachines consist of a porous sphere made of silica. Their surfaces carry various components with specific functions. Among them is the enzyme urease, a protein that reacts with urea found in urine, enabling the nanoparticle to propel itself. Another crucial component is radioactive iodine, a radioisotope commonly used for the localized treatment of tumors.

The research, led by the Institute for Bioengineering of Catalonia (IBEC) and CIC biomaGUNE in collaboration with the Institute for Research in Biomedicine (IRB Barcelona) and the Autonomous University of Barcelona (UAB), paves the way for innovative bladder cancer treatments. These advancements aim to reduce the length of hospitalization, thereby implying lower costs and enhanced comfort for patients.

"With a single dose, we observed a 90% decrease in tumor volume. This is significantly more efficient given that that patients with this type of tumor typically have 6 to 14 hospital appointments with current treatments. Such a treatment approach would enhance efficiency, reducing the length of hospitalization and treatment costs," explains Samuel Sánchez, ICREA research professor at IBEC and leader of the study.

The next step, which is already underway, is to determine whether these tumors recur after treatment.

In previous research, the scientists confirmed that the self-propulsion capacity of nanorobots allowed them to reach all bladder walls. This feature is advantageous compared to the current procedure where, after administering treatment directly into the bladder, the patient must change position every half hour to ensure that the drug reaches all the walls.

This new study goes further by demonstrating not only the mobility of nanoparticles in the bladder but also their specific accumulation in the tumor. This achievement was made possible by various techniques, including medical positron emission tomography (PET) imaging of the mice, as well as microscopy images of the tissues removed after completion of the study. The latter were captured using a fluorescence microscopy system developed specifically for this project at IRB Barcelona. The system scans the different layers of the bladder and provides a 3D reconstruction, thereby enabling observation of the entire organ.

"The innovative optical system that we have developed enabled us to eliminate the light reflected by the tumor itself, allowing us to identify and locate nanoparticles throughout the organ without prior labelling, at an unprecedented resolution. We observed that the nanorobots not only reached the tumor but also entered it, thereby enhancing the action of the radiopharmaceutical," explains Julien Colombelli, leader of the Advanced Digital Microscopy platform at IRB Barcelona.

Deciphering why nanorobots can enter the tumor posed a challenge. Nanorobots lack specific antibodies to recognize the tumor, and tumor tissue is typically stiffer than healthy tissue.

"However, we observed that these nanorobots can break down the extracellular matrix of the tumor by locally increasing the pH through a self-propelling chemical reaction. This phenomenon favored greater tumor penetration and was beneficial in achieving preferential accumulation in the tumor," explains Meritxell Serra-Casablancas, co-first author of the study and IBEC researcher.

Thus, the scientists concluded that the nanorobots collide with the urothelium as if it were a wall, but in the tumor, which is spongier, they penetrate the tumor and accumulate inside. A key factor is the mobility of the nanobots, which increases the likelihood of reaching the tumor.

In addition, according to Jordi Llop, a researcher at CIC biomaGUNE and co-leader of the study, "The localized administration of the nanorobots carrying the radioisotope reduces the probability of generating adverse effects, and the high accumulation in the tumor tissue favors the radiotherapeutic effect."

"The results of this study open the door to the use of other radioisotopes with a greater capacity to induce therapeutic effects but whose use is restricted when administered systemically," adds Cristina Simó, co-first author of the study.