Engineered nanoparticles made of amorphous silica effectively killed prostate tumors and enhanced anti-tumor immunity in a preclinical study led by investigators at Weill Cornell Medicine and the Cornell College of Engineering, according to a June 15 report. The particles, derived from silicon dioxide, induced several complete remissions of aggressive tumors in mouse models, supporting further investigation for clinical trials.
Originally developed for medical imaging applications, these ultrasmall fluorescent core-shell silica nanoparticles—known as Cornell Prime dots or C' dots—have progressed into advanced-phase clinical trials for image-guided surgery and therapeutic uses. Recent findings indicate that C' dots can exert therapeutic effects against cancer cells while sparing healthy tissue. In the new study published in Cancer Research, researchers evaluated the effects of these particles on mouse models with aggressive prostate cancer. The results showed that the particles make tumor cells highly susceptible to self-destruction and convert an inactive tumor immune environment into one with strong antitumor activity.
"We're very encouraged by these results; a treatment that directly induces tumor-cell death while transforming the immune microenvironment, as this does, would represent a new clinical paradigm," said Dr. Michelle Bradbury, senior author of the study and director of the Molecular Imaging Innovations Institute at Weill Cornell Medicine.
The research was part of a long-term collaboration between Dr. Bradbury's laboratory and that of Dr. Ulrich Wiesner at Cornell College of Engineering and was funded in part by the Parker Institute for Cancer Immunotherapy at Weill Cornell Medicine. The C' dots pushed prostate tumor cells toward ferroptosis—a self-destruct mode triggered by oxidation—and had immunological impacts including converting T cells and macrophages from inert or suppressive states to robust antitumor activity.
Survival experiments showed that combining C' dots with an immunotherapy called immune checkpoint blockade resulted in complete or near-complete remissions in four out of ten mice; adding CSF-1R blockade increased this to five out of ten complete remissions. "We think there's nothing else out there that has such a strong and durable tumor growth suppressing effect," Bradbury said.
Dr. Jedd Wolchok, co-author on the study, said, "By creating conditions that support a more effective antitumor immune response, these particles may help unlock the full potential of immunotherapy in prostate cancer." Researchers are continuing to explore ultrasmall core-shell silica particles as anticancer therapeutics with plans for future clinical trials.
