New Study Shows Promise of Amorphous Silica Nanoparticles in Fighting Prostate Cancer
Engineered nanoparticles made from amorphous silica are showing effectiveness in targeting prostate tumors and boosting immune responses against them, according to a recent preclinical study conducted by researchers at Weill Cornell Medicine and Cornell’s Duffield College of Engineering.
The particles, which originate from silicon dioxide—commonly found in some foods and fossilized remains of single-celled organisms—have demonstrated the potential to induce complete remissions of aggressive tumors in mouse models. This raises hopes for their future use in clinical trials.
Initially developed for medical imaging, these particles, known as ultrasmall fluorescent core-shell silica nanoparticles or Cornell Prime dots (C’ dots), have advanced into later-stage clinical trials for both image-guided surgery and treatment. Recently, researchers discovered that the C’ dots can have therapeutic effects against cancer cells while leaving healthy cells unharmed.
The findings, published on June 15 in *Cancer Research*, show that in mouse models of aggressive prostate cancer, these particles make tumor cells more vulnerable to a self-destruct process and simultaneously transform the typically inactive prostate tumor immune microenvironment into an active one, enhancing the effectiveness of other immunotherapies.
“We’re very encouraged by these results,” noted Dr. Michelle Bradbury, the senior author of the study. “A treatment that induces tumor-cell death while also changing the immune environment would represent a shift in clinical approaches.”
This study stems from a longstanding collaboration between Bradbury’s group and Ulrich Wiesner’s lab, and it received partial funding from the Parker Institute for Cancer Immunotherapy at Weill Cornell.
An interesting aspect of the C’ dots is their ability to push prostate tumor cells into a self-destruct mode called “ferroptosis.” This process involves the excessive oxidation of molecules within the cells, particularly fat-related ones that constitute cell membranes. It’s somewhat unclear how the C’ dots initiate this effect, but they seem to transport positively charged iron ions from the bloodstream into tumor cells, potentially triggering this oxidation process.
The C’ dots also appear to significantly influence immune responses within the tumor environment, converting various immune cells from inactive to active, which leads to better sensitivity to existing anticancer immunotherapies. The research indicates notable metabolic disruptions within the tumor microenvironment due to the silica particles.
Targeted specifically to prostate tumor cells via a molecule that binds to a surface protein called PSMA, the particles did not show toxicity even in other tissues like the spleen where they briefly accumulated.
“It almost seems unbelievable to see so many effects happening at once, and only in tumors,” Wiesner remarked. “It makes me wonder if the widespread presence of ultrasmall silica in our environment has established some biological connection we’re only beginning to uncover.”
In survival experiments involving mice with aggressive prostate cancer, researchers found that using C’ dots in conjunction with an immunotherapy called immune checkpoint blockade led to complete or near-complete remissions in four out of ten mice, while adding another treatment aimed at tumor-associated macrophages improved this to five out of ten complete remissions.
“We believe there’s nothing else like this that offers such a lasting suppressive effect on tumor growth,” Bradbury said.
“One of the most intriguing aspects of this research is how it combines direct tumor-cell killing with a broad remodeling of the immune environment,” mentioned Dr. Jedd Wolchok, a co-author of the study. “This could enhance the effectiveness of immunotherapy in prostate cancer, where achieving durable responses has been challenging.”
Bradbury and her team also recognized the contributions of co-first authors Nabil Siddiqui, Dr. Li Zhang, and Gabriel DeLeon, though many others played vital roles in the experiments and analysis, including graduate students from Wiesner’s lab.
“This study reflects years of teamwork across multiple labs, and it wouldn’t have been possible without the dedication of everyone involved,” Bradbury added.
The researchers aim to continue exploring these silica nanoparticles as a new class of anticancer therapies that could influence inflammatory, immune, and metabolic pathways, with plans to assess their safety and effectiveness in upcoming clinical trials.
The study received financial backing from various sources, including the Department of Defense and the National Cancer Institute, part of the National Institutes of Health.
Dr. Michelle Bradbury and Ulrich Wiesner are listed as inventors on patents associated with this technology.
