Cornell-developed “prime dots” trigger immune activation by reshaping the tumor microenvironment.
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The recent study, conducted by researchers from Weill Cornell Medicine and Cornell Engineering, demonstrates an unforeseen capability to activate the immune system against melanoma, significantly enhancing the efficacy of cancer immunotherapy by using a class of extremely small fluorescent core-shell silica nanoparticles developed at Cornell University.
The study was published in Nature Nanotechnology.
The particles, referred to as Cornell prime dots, or C’dots, have previously undergone testing in human clinical trials for use as a cancer diagnostic tool and a drug delivery mechanism.
The study reveals that these nanoparticles can actually reprogram the tumor microenvironment (TME), converting immune-resistant tumors into those that respond much more effectively to treatment.
It’s a very surprising discovery. C’dots on their own – without any pharmaceutical entity on their surface – induce a whole range of antitumoral effects in the TME of melanoma models that, in part, are entirely unexpected.
Ulrich Wiesner, Professor, Department of Design Tech, College of Architecture, Art and Planning, Cornell University
The research expands upon a 2016 study in which the team identified that C’dots induce ferroptosis, a type of regulated cell death, in cancer cells and animal models, leading to a decrease in tumor growth without the use of traditional chemotherapy.
The latest study suggests that the particles have effects that extend beyond directly targeting tumor cells.
Employing aggressive, immunotherapy-resistant melanoma models, the researchers discovered that C’dots trigger various antitumor effects concurrently: They activate innate immune responses via pattern-recognition receptors, inhibit cancer cell proliferation by causing cell-cycle arrest, diminish immune suppression within the tumor microenvironment (TME), and reprogram essential immune cells – such as T cells and macrophages – to more effectively combat cancer.
This platform is not simply acting as a passive carrier or delivery vehicle; these nanoparticles are intrinsically active therapeutic agents. Rather than targeting a single pathway, these particles engage multiple mechanisms simultaneously and in ways that conventional therapies cannot easily achieve.
Dr. Michelle Bradbury, Study Corresponding Author and Professor, Radiology, Radiation Oncology and Neuroscience, Feil Family Brain and Mind Research Institute, Weill Cornell
Aggressive solid tumor microenvironments (TMEs), such as those associated with melanoma, prostate, breast, and colon cancers, are classified as “cold.” This classification indicates that they do not elicit robust immune responses and frequently exhibit resistance to immunotherapy.
The research indicates that C’dots can transform these cold tumors into “hot” ones, fostering an inflammatory milieu that enhances the efficacy of immunotherapies.
In mouse models, a novel combinatorial treatment approach that involves the administration of C’dots in conjunction with immunotherapies targeting both an immune checkpoint and cytokines – molecules that play a crucial role in regulating immune responses – resulted in a notable survival benefit when compared to immunotherapy alone.
The investigators discovered that the treatments produced a synergistic effect, where the nanoparticles altered the immune landscape and augmented the effectiveness of the immunotherapies, resulting in a significantly more potent impact.
“Many aggressive tumors are resistant to immunotherapies alone. What these nanoparticles do is mitigate inhibitory activities within the TME, in turn suppressing tumor growth and limiting resistance,” said Bradbury.
The results indicate that the methodology may have applications that extend far beyond melanoma. Wiesner remarked that the team at Weill Cornell Medicine detected comparable immune-activating effects of C’dots in various other solid tumor models, such as prostate and ovarian cancers, suggesting that these findings could reveal a more profound biological narrative.
“From the early stages of evolution, biological organisms have been exposed to nanoparticulate silica on the inside, including through intake of foods like grasses and seaweed. The hypothesis is that cancer pushes your system out of equilibrium, away from homeostasis. But silica pushes back, and the reason it’s multifactorial is because over millions of years, organisms developed various mechanisms by which silica can basically maintain homeostasis,” said Wiesner, citing an earlier study on oral delivery of C’dots.
Although the concept is still speculative, Wiesner and team are starting to investigate the hypothesis in collaboration with researchers from Cornell’s nutritional sciences department.
Journal Reference:
Bradbury, S. M., et al. (2025) An ultrasmall core–shell silica nanoparticle improves antitumor immunity and survival by remodelling suppressive melanoma microenvironments. Nature Nanotechnology. DOI: 10.1038/s41565-025-02083-z.