New nanomaterial kills cancer cells via oxidative stress

Scientists at Oregon State University have developed a new nanomaterial that triggers a pair of chemical reactions inside cancer cells, killing the cells via oxidative stress while leaving healthy tissues alone.

The study led by Oleh and Olena Taratula and Chao Wang of the OSU College of Pharmacy was published this week in Advanced Functional Materials.

The findings advance the field of chemodynamic therapy or CDT, an emerging treatment approach based on the distinctive biochemical environment found in cancer cells. Compared to healthy tissues, malignant tumors are more acidic and have elevated concentrations of hydrogen peroxide, the scientists explain.

Conventional CDT works by using the tumor microenvironment to trigger the chemical production of hydroxyl radicals: molecules, made up oxygen and hydrogen, with an unpaired electron. These reactive oxygen species are able to damage cells through oxidation by stealing electrons from molecules like lipids, proteins and DNA.

Recent chemodynamic therapy designs have been able to use tumor conditions to catalyze production of another reactive oxygen species, singlet oxygen, so named because it has one electron spin state rather than the three states found in the more stable oxygen molecules in the air.

"However, existing CDT agents are limited," Oleh Taratula said. "They efficiently generate either radical hydroxyls or singlet oxygen but not both, and they often lack sufficient catalytic activity to sustain robust reactive oxygen species production. Consequently, preclinical studies often only show partial tumor regression and not a durable therapeutic benefit."

In this paper, the scientists present a novel CDT nanoagent, an iron-based metal-organic framework or MOF, able to generate both compounds for more effective treatment, and with superior catalytic efficiency. The MOF showed potent toxicity in multiple cancer cell lines and negligible harm to noncancerous cells.

When we systemically administered our nanoagent in mice bearing human breast cancer cells, it efficiently accumulated in tumors, robustly generated reactive oxygen species and completely eradicated the cancer without adverse effects. We saw total tumor regression and long-term prevention of recurrence, all without seeing any systemic toxicity."

Olena Taratula, OSU College of Pharmacy

Before this treatment can be tested in humans, the research team plans to evaluate its therapeutic efficacy in various cancer types, including aggressive pancreatic cancer, to demonstrate its broad applicability across different malignancies.

Oregon State's Kongbrailatpam Shitaljit Sharma, Yoon Tae Goo, Vladislav Grigoriev, Constanze Raitmayr, Ana Paula Mesquita Souza and Manali Parag Phawde also contributed to the research, which was funded by the National Cancer Institute of the National Institutes of Health and the Eunice Kennedy Shriver National Institute of Child Health and Human Development.