Silica nanoparticles eliminate aggressive prostate cancer in mice
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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