Targeted Corrole Therapy Safely Shrinks HER2-Positive Breast Cancer Tumors

A corrole is an aromatic organic chemical, whose structure is in the form of the corrin ring, which is also present in vitamin B12. The ring consists of nineteen carbon atoms, with four nitrogen atoms in the core of the molecule. Corroles containing sulfonated gallium(III) are intensely fluorescent compounds that spontaneously assemble with carrier proteins to undergo cell entry.

In the current study published in the April 1, 2009, online edition of the Proceedings of the [U.S.] National Academy of Sciences (PNAS) investigators combined gallium(III) corroles with a carrier protein that specifically targeted the HER2 receptor. They reported that systemic delivery of this protein-corrole complex to mice carrying human HER2-positive tumors resulted in tumor accumulation, which could be visualized in vivo owing to intensely red corrole fluorescence. Targeted delivery in vivo led to tumor cell death while normal tissue was spared.

These findings contrasted with the effects of doxorubicin, which often caused cardiac damage during therapy and required direct intratumoral injection to yield similar levels of tumor shrinkage compared with the systemically delivered corrole. The targeted complex shrank tumors at greater than five times a lower dose than untargeted systemic doxorubicin, and the corrole did not damage heart tissue. Complexes remained intact in serum, and the carrier protein elicited no detectable immunogenicity.

"We looked at three groups of mice with human tumors," explained senior author Dr. Lali Medina-Kauwe, assistant professor of medicine at the University of California, Los Angeles (USA). "In one, we introduced just the protein carrier, without the corrole; tumor growth in those mice did not change. In other mice, we gave the corrole without the carrier protein; this led to some tumor suppression. But it was the last group; the ones that got the corrole with the carrier protein that experienced the most therapeutic effect. One of the beauties of targeting is that we can go after metastatic tumors that are too small to be seen."

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