Cancer Tumors Reduced by 90% Using Nanorobots
By INSTITUTE FOR BIOENGINEERING OF
CATALONIA (IBEC)
A recent study reveals a novel treatment for bladder cancer using urea-powered nanorobots, which have successfully reduced tumor size in mice by 90%. This innovative approach promises to make treatment more efficient and less burdensome for patients. (Artist’s concept.) Credit: SciTechDaily.com
Bladder cancer has one of the highest
incidence rates in the world and ranks as the fourth most common tumor in men.
Despite its relatively low mortality rate, nearly half of bladder tumors
resurface within 5 years, requiring ongoing patient monitoring. Frequent
hospital visits and the need for repeat treatments contribute to making this
type of cancer one of the most expensive to cure.
While current treatments involving direct
drug administration into the bladder show good survival rates, their
therapeutic efficacy remains low. A promising alternative involves the use of
nanoparticles capable of delivering therapeutic agents directly to the tumor.
In particular, nanorobots—nanoparticles endowed with the ability to self-propel
within the body—are noteworthy.
Breakthrough in Nanorobotics for Bladder Cancer Treatment
Now, a study published in the prestigious
journal Nature Nanotechnology reveals how a research team
successfully reduced the size of bladder tumors in mice by 90% through a single
dose of urea-powered nanorobots.
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
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.
A Fantastic Voyage Into the Bladder
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 labeling, 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.
Years of Work and Spin-Off Company
The study consolidates the results of over
three years of collaborative efforts between various institutions. Part of the
data stems from the doctoral theses of Meritxell Serra and Ana Hortelao, both
researchers in IBEC’s Smart nano-bio-devices group, led by Sánchez. It also
includes the thesis of Cristina Simó, co-first author of the study, who
conducted her predoctoral research in the Radiochemistry and Nuclear Imaging
Lab led by Jordi Llop at CIC biomaGUNE. The expertise of Esther Julián´s group
at the UAB in the animal model of the disease is an additional contribution.
Moreover, the project has received funding from the European Research Council
(ERC) and the” la Caixa” Foundation.
The technology underlying these nanorobots,
which Samuel Sánchez and his team have been developing for over seven years,
has recently been patented and serves as the foundation for Nanobots
Therapeutics, a spin-off of IBEC and ICREA established in January 2023.
The company, founded by Sánchez, acts as a
bridge between research and clinical application: “Securing robust funding for
the spin-off is crucial to continue advancing this technology and, if all goes
well, bring it to market and society. In June, just 5 months after the creation
of Nanobots Tx, we successfully closed the first round of funding, and we are
enthusiastic about the future,” highlights Sanchez.
Technological Innovation in Microscopy To Locate
Nanorobots
Working with nanorobots has posed a
significant scientific challenge in bioimaging techniques for visualizing these
elements in tissues and the tumor itself. Common non-invasive clinical
techniques, such as PET, lack the necessary resolution to locate these very
small particles at a microscopic level. Therefore, the Scientific Microscopy
Platform at IRB Barcelona employed a microscopy technique using a sheet of
laser light to illuminate samples, allowing the acquisition of 3D images
through light scattering upon interaction with tissues and particles.
Upon observation that the tumor itself
scattered part of the light, generating interference, the scientists developed
a new technique based on polarized light that cancels out all scattering from
the tumor tissue and cells. This innovation enables the visualization and
location of nanorobots without the need for prior tagging with molecular
techniques.
Reference: “Radionuclide therapy with
accumulated urease-powered nanobots reduces bladder tumor size in an orthotopic
murine model” 15 January 2023, Nature Nanotechnology.
DOI:
10.1038/s41565-023-01577-y