Particle Designed to Attack Cancer, Enhance MRI

Lending new meaning to the battlefield term search and destroy, cancer researchers are developing powerful agents designed to simultaneously reveal tumors and attack them. Cedars-Sinai is pioneering one such agent, aimed at an aggressive form of breast cancer.

Fluorescent images of HER2+ breast cancer cells in mouse models before (left) and after treatment with the HerMn nanoparticle show collapse of the cellular structure caused by HerMn.

In a multicenter project, a team led by Lali K. Medina-Kauwe, PhD, research scientist in the Cedars-Sinai Samuel Oschin Comprehensive Cancer Institute and associate professor in the Department of Biomedical Sciences, assembled a new type of anti-cancer particle. In mouse models, the particle was shown to enhance magnetic resonance imaging (MRI) of breast tumors and also kill cancer cells.

Because the particle was delivered only to the tumors, it did not appear to pose the risk of damaging heart tissue — an issue with certain traditional chemotherapies, according to the researchers.

Although the study has not yet been performed with human subjects, the data pointed to a potential two-pronged attack on breast cancer that could produce less collateral damage than therapies in current clinical use. The study was published Nov. 10 in the Journal of Controlled Release.

Researchers created their anti-cancer agent using nanotechnology, which involves engineering tiny particles from about 1 to 100 nanometers in size for medical uses. The resulting agents are known as nanoparticles.

The team assembled a nanoparticle, which they named HerMn, by attaching a genetically engineered protein known as HerPBK10 to a synthetic compound containing manganese, which enhances magnetic resonance imaging. HerPBK10, developed in Medina-Kauwe's laboratory, targets and penetrates HER2+ tumors, a highly aggressive type of breast cancer that is resistant to standard chemotherapy and has a poor prognosis.

Mouse models of HER2+ breast cancer that were injected with the HerMn nanoparticle showed a marked reduction in tumor volume versus controls, without apparent damage to cardiac cells, the researchers reported. Magnetic resonance images of tumors in these mice also showed greater contrast, they said.

The study is part of the emerging field of multifunctional therapeutics or "theranostics," which aims to engineer into a single particle the capacity to detect, diagnose and treat disease. It builds on Medina-Kauwe's previous work, in which she has combined HerPBK10 with a variety of synthetic compounds, including one that enhanced fluorescent imaging of Her2+ tumors.

"We are currently testing this technology for addressing resistant and metastatic tumors, including brain metastases," Medina-Kauwe said. The technology is being further developed for translation into the clinic by Eos Biosciences Inc., a company that Medina-Kauwe co-founded, she added.

Other Cedars-Sinai researchers from the Department of Biomedical Sciences, Biomedical Imaging Research Institute and Heart Institute contributed to the Journal of Controlled Release article. Also contributing were researchers from several institutions, including Daegu Gyeongbuk Institute of Science and Technology in Daigu South Korea; Technion-Israel Institute in Haifa; the California Institute of Technology in Pasadena; and Children's Hospital of Los Angeles. For the complete author list, please see the citation below.

Citation: Journal of Controlled Release. 2015 Nov. 10: A corrole nanobiologic elicits tissue-activated MRI contrast enhancement and tumor-targeted toxicity.