Researchers at Weill Cornell Medicine and Cornell Engineering have developed tiny silica nanoparticles that can directly destroy prostate tumors while simultaneously awakening the body's immune system, according to a new preclinical study published in Cancer Research. In mouse models of aggressive prostate cancer, the treatment produced several complete tumor remissions when combined with immunotherapy.
The nanoparticles, known as ultrasmall fluorescent core-shell silica nanoparticles or Cornell Prime dots (C' dots), were originally created for medical imaging and have already advanced into late-stage clinical trials for image-guided surgery. But researchers discovered the particles themselves can selectively damage cancer cells while leaving healthy cells largely unharmed.
"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 senior author Dr. Michelle Bradbury, director of the Molecular Imaging Innovations Institute at Weill Cornell Medicine.
The particles trigger a specialized form of cell death called ferroptosis, driven by overwhelming oxidation inside cells. Evidence suggests the particles collect positively charged iron ions from the bloodstream and transport them into tumor cells, where the iron fuels intense oxidation that destroys cell membranes.
Beyond directly killing tumor cells, the nanoparticles reshaped the immune environment surrounding the cancer — transforming it from an immune-resistant "cold" state into an immune-active "hot" state. T cells, macrophages, and other immune cells near the tumors shifted from inactive states into active cancer-fighting cells.
The most dramatic results came from combination therapy. While C' dots or immunotherapy alone modestly improved survival, combining the nanoparticles with an immune checkpoint blockade produced complete or nearly complete remissions and indefinite survival in 4 out of 10 mice. Adding a third treatment targeting tumor-associated macrophages increased complete remissions to 5 out of 10 mice.
"We think there's nothing else out there that has such a strong and durable tumor growth suppressing effect," Dr. Bradbury said.
The research team is now working toward human clinical trials to evaluate the safety and effectiveness of the treatment.
