Nanoparticle Strategy Utilizes Tumors’ Copper for Cancer Treatment

Researchers have developed a novel nanoparticle-based strategy aimed at advancing a promising cancer treatment approach by utilizing tumors’ own copper supply to trigger cancer cell death. The study, conducted by researchers at Guizhou Medical University and published in Biomedical Analysis, focuses on cuproptosis—a form of cell death caused by copper disrupting cancer cell survival mechanisms.

Cuproptosis has been considered as a potential cancer treatment; however, earlier methods relying on external copper raised concerns about toxicity to healthy tissues. The new system addresses this issue by delivering a copper-binding agent directly to the cancer cells, leveraging the copper already present inside tumors.

To develop this system, researchers engineered biodegradable nanoparticles using PLGA-PEG, a material recognized for its safety and ability to degrade within the body. They enhanced the nanoparticles’ surface with iRGD, a tumor-penetrating peptide, to direct the particles toward the cancer cells. The nanoparticles were infused with TPEN, a compound that binds to metal ions, including copper.

The resulting formulation, known as TPEN@1%-iPPN, was created to specifically deliver TPEN into tumor cells. Laboratory tests revealed that the nanoparticles measured approximately 80 nanometers in size and remained stable under conditions mimicking the bloodstream. They also allowed gradual TPEN release over a 72-hour period for sustained exposure within the tumor.

Further testing assessed the benefit of the iRGD coating in enhancing nanoparticle targeting to cancer cells. In experiments using 4T1 breast cancer cells, the targeted nanoparticles were absorbed by cancer cells significantly more than those lacking the targeting feature.

The study found that a 1% iRGD modification offered an optimal balance between cancer-cell targeting and nanoparticle stability. The researchers also evaluated the nanoparticles’ capacity to damage cancer cells while minimizing effects on normal cells. The targeted nanoparticles exhibited stronger toxicity against 4T1 breast cancer cells compared to non-targeted versions, causing notably less harm to normal human endothelial cells than untargeted TPEN.

Dr. Ying Chen, the study’s corresponding author, stated that this strategy of utilizing endogenous copper represents a promising pathway to enhance selectivity and decrease systemic side effects commonly associated with metal-based cancer therapies. “We have provided solid proof-of-concept at the cellular level, which we hope will inspire further research into cuproptosis-based nanomedicine,” she remarked.

Although the findings suggest a new potential direction for cancer nanomedicine, experts caution that significant challenges remain before this approach could be implemented as a treatment option for patients. According to Dr. Harshad Kulkarni, chief medical advisor for BAMF Health, while the approach is scientifically promising due to its exploitation of metabolic vulnerabilities present in many cancer cells, the field is at an early stage.

He emphasized that researchers must demonstrate safe control over copper-related treatments, identify responsive cancer types, and find biomarkers that confirm proper treatment functioning. “The central challenge will be achieving tumor selectivity. Copper is vital for normal cellular function, thus altering copper concentrations across the body could lead to significant toxicity,” he added.

Dr. Kulkarni pointed out that future studies should consider potential side effects, including impacts on major organs, and assess whether cancer cells could adapt by changing their copper handling methods. While the approach shows promise beyond breast cancer, its efficacy may depend more on the specific biological traits of each tumor than on the cancer’s location. Additional research will be crucial to determine if this laboratory approach can eventually lead to safe and effective patient therapies.

For inquiries about this article, contact Newsweek editors Kara Dolman and Gray R. Thomas.