Nanoparticles Destroy Aggressive Prostate Tumors While Simultaneously Strengthening the Immune System

Researchers have developed tiny silica nanoparticles that can directly destroy prostate tumors while simultaneously activating the body’s own immune system to fight cancer. This is according to a new preclinical study led by scientists at Weill Cornell Medicine and the Cornell Duffield College of Engineering. In mouse models of aggressive prostate cancer, the targeted particles led to several cases of complete tumor remission, providing promising evidence that this approach could eventually move into clinical trials in humans.

What is Prostate Cancer?

Prostate cancer is the most common cancer in men and originates in the prostate, a walnut-sized gland located below the bladder that produces part of the seminal fluid. The risk of developing the disease increases significantly with age: Most diagnoses are made after age 65, while prostate cancer is comparatively rare in men under 50. In addition to age, the most important risk factors include a family history of the disease and certain genetic mutations. In its early stages, prostate cancer often causes no symptoms and is frequently detected during a screening exam. If symptoms do occur, they may include, among other things, a frequent urge to urinate—especially at night—a weak urine stream, difficulty urinating, blood in the urine or semen, and pain in the pelvic or lower back area. However, these symptoms can also be caused by benign prostate conditions and do not necessarily indicate cancer. If prostate cancer is detected early, the chances of recovery are very good in many cases. Researchers are constantly searching for strategies to combat this common form of cancer in men.

Tiny Nanoparticles With a Dual Strategy for Fighting Cancer

The nanoparticles, made from amorphous silica—a form of silica that occurs naturally in food and the fossilized remains of microscopic organisms—appear to attack prostate cancer in several ways simultaneously. The nanoparticles, known as ultra-small fluorescent core-shell silica nanoparticles or “Cornell Prime Dots” (C’-Dots), were originally developed to improve medical imaging. They are already in advanced clinical trials for image-guided surgery and other therapeutic applications. Recently, researchers discovered that the particles themselves can selectively damage cancer cells while leaving healthy cells largely unharmed.

In the new study, published in Cancer Research, a journal of the American Association for Cancer Research, the team tested the nanoparticles on mice with aggressive prostate cancer. They found that the particles made the tumor cells extremely susceptible to a form of self-destruction while simultaneously transforming the tumor microenvironment from an immune-resistant “cold” state to an immune-active “hot” state. This change could significantly improve the effectiveness of existing immunotherapies.

“We are very encouraged by these results; a treatment that directly induces tumor cell death while simultaneously altering the immunological microenvironment, as is the case here, would represent a new clinical paradigm,” said lead author Dr. Michelle Bradbury, Endowed Professor of Imaging Research in Radiology and Director of the Molecular Imaging Innovations Institute at Weill Cornell Medicine, as well as a neuroradiologist at NewYork-Presbyterian/Weill Cornell Medical Center. The work is part of a long-standing collaboration between Dr. Bradbury’s lab and the lab of co-author Dr. Ulrich Wiesner, the Spencer T. Olin Professor in the Department of Materials Science and Engineering and a professor in the Department of Design Tech at the College of Architecture, Art, and Planning. The research was partially supported by the Parker Institute for Cancer Immunotherapy at Weill Cornell Medicine.

How the Silica Particles Kill Cancer Cells

One of the study’s most remarkable findings concerns a process called ferroptosis—a form of programmed cell death that was only described in detail a few years ago. Unlike the better-known apoptosis, in which cells break down in a controlled and orderly manner, ferroptosis is triggered by iron-dependent oxidative stress. This process generates large amounts of highly reactive oxygen compounds (reactive oxygen species, ROS), which primarily attack the polyunsaturated fatty acids in the cell membranes. Through this process, known as lipid peroxidation, the cell membranes lose their stability and function until the cancer cells are ultimately irreversibly damaged and die.

It is particularly interesting that many cancer cells—including aggressive prostate tumors—already exhibit elevated iron concentrations and increased susceptibility to oxidative stress due to their altered metabolism. At the same time, they often develop resistance to classic forms of cell death such as apoptosis. This is precisely where ferroptosis could offer a therapeutic advantage, as it utilizes a completely different mechanism and can therefore also target tumor cells that are less sensitive to conventional treatments.

Researchers do not yet fully understand how the ultra-small silicon dioxide nanoparticles trigger this process. However, their findings suggest that the particles can absorb positively charged iron ions from the bloodstream and transport them specifically into the tumor cells. There, the iron could promote chemical reactions that generate large amounts of reactive oxygen species. At the same time, the nanoparticles appear to overwhelm the cancer cells’ natural antioxidant defense mechanisms, causing oxidative damage to rapidly intensify and ultimately triggering ferroptosis. Another potential advantage of this mechanism is that the dying tumor cells release signaling molecules that alert the immune system.

Revitalizing the Immune System

The nanoparticles not only directly killed tumor cells but also altered the immune environment surrounding the cancer tissue. The researchers observed that T cells, macrophages, and other immune cells near the tumors transitioned from an inactive or immunosuppressive state to active, cancer-fighting cells. The nanoparticles also ensured that the tumors responded significantly better to approved immunotherapies. At the same time, they disrupted metabolic processes in various cell types within the tumor microenvironment, which further slowed tumor growth. To ensure that the treatment reached the prostate cancer cells, the team added a targeting molecule that recognizes PSMA, a protein found on the surface of prostate tumor cells. Although some particles temporarily accumulated in other organs such as the spleen, the researchers found no signs of toxicity outside the tumors.

“It seems unreal—how is it possible that we observe all these effects not through a single signaling pathway, but simultaneously and exclusively in tumors and not in healthy tissue?” said Dr. Wiesner. “I wonder whether the very early and ubiquitous presence of ultrafine silica particles in the environment and in foods such as leafy vegetables or grains has established a connection to biology that we are only now beginning to grasp.”

The Combination Therapy Yielded the Strongest Results

The most dramatic results came from survival studies in mice with aggressive prostate cancer. On their own, both the C’dots and immunotherapy only marginally improved survival compared to no treatment. However, combining the nanoparticles with an immune checkpoint blockade therapy led to complete or near-complete remissions and indefinite survival in four out of ten mice. By adding a third therapy—known as CSF-1R blockade, which targets tumor-associated macrophages—the number of complete remissions rose to five out of ten mice.

“We believe there is nothing comparable that has such a powerful and sustained effect on suppressing tumor growth,” said Dr. Bradbury. “One of the most fascinating aspects of this work is the interplay between direct tumor cell killing and comprehensive remodeling of the immune system,” said the study’s co-author, Dr. Jedd Wolchok, Meyer Director of the Sandra and Edward Meyer Cancer Center, professor of medicine at Weill Cornell Medicine, director of the Parker Institute for Cancer Immunotherapy at the Weill Cornell Medicine Meyer Cancer Center, and oncologist at NewYork-Presbyterian/Weill Cornell Medical Center. “By creating conditions that support a more effective antitumor immune response, these particles could help unlock the full potential of immunotherapy in prostate cancer, where durable response rates have been difficult to achieve in the past.”

The Next Step is Clinical Trials in Humans

Dr. Bradbury also acknowledged the work of the study’s co-first authors—physicians Nabil Siddiqui, Li Zhang, and Gabriel DeLeon, who led many of the biological, mechanistic, and translational studies—as well as doctoral students Nada Naguib and Rachel Lee from Dr. Wiesner’s lab, whose meticulous synthesis and characterization of the nanoparticles were crucial to the project. “This study reflects years of collaboration across multiple laboratories and would not have been possible without the dedication, creativity, and perseverance of this outstanding research team, which has helped advance science,” she said.

The research team continues to investigate these ultra-small silica core-shell particles as a potential new class of cancer therapies capable of simultaneously influencing inflammatory, immune, and metabolic pathways. Their long-term goal is to evaluate the safety and efficacy of the treatment in clinical trials involving human subjects. Dr. Michelle Bradbury and Dr. Ulrich Wiesner are inventors on patents related to the technology described in this study.