By Morgan Nwanguma
Engineered silica nanoparticles have shown an extraordinary ability to destroy prostate cancer tumours while simultaneously activating the immune system, leading to complete tumour remissions in several laboratory mice. The findings, from a new preclinical study, suggest the technology could pave the way for a powerful new treatment strategy against prostate cancer and potentially enhance the effectiveness of existing immunotherapies.
Scientists from Weill Cornell Medicine and the Cornell Duffield College of Engineering developed the microscopic particles, known as Cornell Prime dots (C’ dots), which are made from amorphous silica – a naturally occurring form of silicon dioxide found in foods and the fossilized remains of tiny organisms. Originally designed to improve medical imaging, the nanoparticles have already progressed into late-stage clinical trials for image-guided surgery and other therapeutic applications.
The latest study, published in Cancer Research on June 15, revealed that the nanoparticles do far more than assist with imaging. Researchers found that they can selectively target and destroy prostate cancer cells while largely sparing healthy tissue.
In mouse models of aggressive prostate cancer, the nanoparticles triggered a process known as ferroptosis, a specialised form of cell death caused by overwhelming oxidative damage within cells. During ferroptosis, oxidation attacks vital cellular components, particularly the fatty molecules that form cell membranes, ultimately causing cancer cells to collapse and die.
Although the precise mechanism remains under investigation, researchers believe the nanoparticles may capture positively charged iron ions from the bloodstream and carry them into tumour cells. The iron then fuels intense oxidative stress, driving the ferroptosis process.
Beyond directly killing cancer cells, the nanoparticles dramatically altered the tumour microenvironment. Prostate tumours are often considered “cold,” meaning they resist immune attack. Treatment with the silica particles transformed these tumours into “hot” tumours by stimulating immune activity around the cancer.
The study showed that T cells, macrophages and other immune cells shifted from inactive or suppressive states into active cancer-fighting modes. Researchers also observed widespread disruption of metabolic pathways within the tumour environment, further slowing tumour growth and enhancing anti-cancer activity.
Senior author Dr. Michelle Bradbury, Professor of Imaging Research in Radiology at Weill Cornell Medicine and Director of the Molecular Imaging Innovations Institute, described the findings as highly encouraging.
“We’re very encouraged by these results; a treatment that directly induces tumour-cell death while transforming the immune microenvironment, as this does, would represent a new clinical paradigm,” she said.
To ensure precise targeting, the research team attached a molecule that recognizes prostate-specific membrane antigen (PSMA), a protein commonly found on prostate cancer cells. This targeting system enabled the nanoparticles to concentrate within tumours while producing no detectable toxic effects in healthy organs, despite some temporary accumulation in tissues such as the spleen.
The research emerged from a long-standing collaboration between Dr. Bradbury’s laboratory and the laboratory of co-corresponding author Dr. Ulrich Wiesner, Professor of Materials Science and Engineering at Cornell University.
Dr. Wiesner expressed surprise at the breadth of the nanoparticles’ effects.
“It seems unreal – how is it possible that rather than a single pathway we see all these effects happening simultaneously and only in tumours and not in healthy tissues?” he said. “I have to wonder whether ultrasmall silica’s very early and ubiquitous presence in the environment and foods like leafy greens or cereal grains has given it a connection to biology that we’re only beginning to glimpse.”
The most impressive results emerged when the nanoparticles were combined with immunotherapy. While treatment with either C’ dots or immune checkpoint blockade alone produced only modest improvements in survival, the combination generated complete or near-complete tumour remissions in four out of ten mice, with long-term survival observed.
Adding a third therapy known as CSF-1R blockade, which targets tumour-associated macrophages, increased complete remissions to five out of ten mice.
According to Dr. Bradbury, the durability of the response sets the treatment apart from many existing approaches.
“We think there’s nothing else out there that has such a strong and durable tumour growth suppressing effect,” she said.
Study co-author Dr. Jedd Wolchok, Director of the Parker Institute for Cancer Immunotherapy at Weill Cornell Medicine, noted that the nanoparticles’ ability to combine direct tumour destruction with broad immune activation could help overcome one of prostate cancer’s greatest treatment challenges.
“By creating conditions that support a more effective antitumor immune response, these particles may help unlock the full potential of immunotherapy in prostate cancer, where durable responses have historically been difficult to achieve,” he said.
The investigators credit years of multidisciplinary collaboration for the breakthrough and highlighted the contributions of lead researchers Drs. Nabil Siddiqui, Li Zhang and Gabriel DeLeon, as well as graduate students Nada Naguib and Rachel Lee, whose work on nanoparticle design and characterization was critical to the project.
Researchers are now continuing to explore the therapeutic potential of these ultrasmall silica nanoparticles, which appear capable of simultaneously influencing cancer cell survival, immune responses and tumour metabolism. Their ultimate goal is to advance the technology into human clinical trials to determine whether the promising results seen in animals can be replicated in patients with prostate cancer.
If successful, the approach could represent a new generation of cancer therapies that attack tumours on multiple fronts at once, offering fresh hope for patients with hard-to-treat cancers.
The research was financed by the Department of Defence (PC220534); the National Cancer Institute, part of the National Institutes of Health, through grant numbers R01CA253658, R01CA243085, U54CA199081, the Cancer Centre Support Grant (P30 CA008748), and Cycle for Survival/Parker Institute funding.
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