A preclinical study published on June 15 in Cancer Research reports that ultrasmall fluorescent core-shell silica nanoparticles (C' dots) induced ferroptosis in prostate tumor cells and altered the tumor immune microenvironment in mouse models.
Key Findings
- C' dots triggered ferroptosis, a form of cell death involving lipid oxidation, in prostate tumor cells.
- The particles remodelled the immune microenvironment, activating T cells and macrophages.
- No toxicity was observed in non-tumor tissues, including the spleen.
Survival Experiments
- C' dots alone moderately extended survival in mouse models.
- Immune checkpoint blockade therapy alone also extended survival to a modest degree.
- The combination of C' dots with immune checkpoint blockade resulted in complete remission in 4 of 10 mice.
- Adding CSF-1R blockade, which targets tumor-associated macrophages, yielded complete remission in 5 of 10 mice.
Mechanisms
- C' dots appear to carry positively charged iron ions into tumor cells, catalyzing ferroptosis.
- The particles triggered immune remodeling, converting T cells, macrophages, and other immune cells from inert or suppressive states to antitumor-active states.
- The particles also induced metabolic disruptions in the tumor microenvironment.
"No toxicity was observed in non-tumor tissues, including the spleen."
Attributions
- Study senior author: Dr. Michelle Bradbury, Weill Cornell Medicine.
- Co-corresponding author: Ulrich Wiesner, Cornell University.
- Co-author: Dr. Jedd Wolchok, Weill Cornell Medicine.
Funding and Disclosures
- Funding sources include the Department of Defense, the National Cancer Institute, the Cancer Center Support Grant, and Cycle for Survival/Parker Institute funding.
- Dr. Michelle Bradbury and Ulrich Wiesner are listed as inventors on patents related to the technology.
Next Steps
- The researchers plan to continue exploring C' dots as a new class of anticancer therapeutics and aim to evaluate their safety and efficacy in clinical trials.