In a preclinical study, researchers used tiny silica nanoparticles to eliminate aggressive prostate cancer in mice. The particles induce a form of cell death called ferroptosis and awaken the immune system, turning "cold" tumors "hot." When combined with two other immunotherapy drugs, the treatment produced complete remissions in 5 out of 10 mice. The team at Weill Cornell Medicine now aims to advance the treatment to human clinical trials.
Silica nanoparticle development
- ▪The nanoparticles, called Cornell Prime dots (C' dots), are made from amorphous silica, a form of silicon dioxide
- ▪C' dots were originally created for medical imaging and have already advanced into late-stage clinical trials for that purpose
- ▪Researchers at Weill Cornell Medicine and Cornell Duffield College of Engineering developed silica nanoparticles to treat prostate cancer
- ▪The nanoparticles were engineered with a targeting molecule that recognizes PSMA, a protein on the surface of prostate tumor cells
Ferroptosis mechanism
- ▪Evidence suggests the nanoparticles collect positively charged iron ions from the blood and deliver them into tumor cells, fueling the oxidation that drives ferroptosis
- ▪Ferroptosis is a type of cell death driven by overwhelming oxidation that damages the fatty molecules in cell membranes
- ▪The silica nanoparticles selectively damage cancer cells by inducing a form of self-destruction called "ferroptosis."
Immune system reactivation
- ▪The nanoparticles make tumors significantly more responsive to approved immunotherapy drugs
- ▪The treatment transforms the tumor environment from an immune-resistant "cold" state into an immune-active "hot" state
- ▪Following treatment, immune cells like T cells and macrophages near the tumors shifted from inactive to active cancer-fighting states
Combination therapy results
- ▪Combining the nanoparticles with an immune checkpoint blockade therapy resulted in complete or nearly complete remissions in 4 out of 10 mice
- ▪Adding a third drug, a CSF-1R blockade, to the combination therapy increased the number of complete remissions to 5 out of 10 mice
- ▪In a preclinical study on mice with aggressive prostate cancer, the nanoparticle treatment produced several complete tumor remissions
- ▪Researchers found no signs of toxicity outside the tumors, though some particles briefly accumulated in organs like the spleen
Human clinical trial plans
- ▪The research team's long-term goal is to evaluate the safety and effectiveness of the silica nanoparticle treatment in human clinical trials
- ▪The study was published on June 15 in Cancer Research, a journal of the American Association for Cancer Research
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