A 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. The research was conducted by investigators at Weill Cornell Medicine and Cornell University.
Study Details and Mechanism
The particles are composed of silicon dioxide and are targeted to prostate cancer cells via a molecule that binds to prostate-specific membrane antigen (PSMA).
According to the researchers, C' dots induce ferroptosis, a form of cell death driven by membrane lipid oxidation. The particles are reported to carry positively charged iron ions into tumor cells, catalyzing this process. Additionally, 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.
Survival and Combination Therapy Results
In mouse models of aggressive prostate cancer:
- C' dots alone moderately extended survival.
- Immune checkpoint blockade therapy alone also modestly extended survival.
- The combination of C' dots with immune checkpoint blockade resulted in complete or near-complete remissions and indefinite survival in 4 out of 10 mice.
- Adding CSF-1R blockade (targeting tumor-associated macrophages) to the combination yielded complete remissions in 5 out of 10 mice.
Safety and Toxicity
The study reported that no toxicity was observed in healthy tissues, including the spleen, where particles accumulated. The researchers previously observed that C' dots can exert therapeutic effects against cancer cells while sparing healthy cells.
Context and Development
C' dots were originally developed for medical imaging and have progressed to advanced-phase clinical trials for image-guided surgery and therapy. Dr. Michelle Bradbury (Weill Cornell Medicine) served as the study's senior author, Ulrich Wiesner (Cornell University) served as co-corresponding author, and Dr. Jedd Wolchok (Weill Cornell Medicine) is a study co-author. Dr. Bradbury and Mr. Wiesner are inventors on patents related to the technology.
Next Steps and Funding
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.
The study was funded by the Department of Defense, the National Cancer Institute, the Cancer Center Support Grant, and the Parker Institute for Cancer Immunotherapy.