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Ovotransferrin as a novel drug-targeting molecule for cancer chemotherapy
Ovotransferrin as a novel drug-targeting molecule for cancer chemotherapy

In spite of the numerous discoveries of new anticancer drugs that work on different intracellular targets, many of these drugs have a considerable drawback as they are nonselective thus causing adverse side effects on normal cells. This study is aimed to explore the potential of ovotransferrin (OTf ) as a carrier molecule to allow specific targeting of anticancer drugs to cancer cells via the transferrin receptor (TfR). Receptor binding assay provided evidence that OTf bind to the transferrin-receptor (TfR) of human colon cancer cells. Two anticancer drugs, carboplatin (CBP) and paclitaxel (PTX) were non-covalently conjugated with OTf, at different mole ratios, through freeze-condensation. The two OTf conjugates showed superior anti-proliferative activities against human colon carcinoma (HCT-116) and human breast carcinoma (MCF-7) cells compared to the activities of free drugs, with OTf-cbp being the most potent conjugate. The conjugates with low drug loading inhibited cell growth more efficient than the high drug-loaded conjugates. Fluorescence staining with acridine orange and propidium iodide showed that HCT-116 cells treated with OTfcbp or OTf-PTX exhibited red fluorescence, indicating that PI entered to the nuclei as the cell membrane lost its integrity. The red fluorescence was accompanied by chromatin condensation and fragmentation indicates apoptosis. The results demonstrate, for the first time, that OTf could be utilized to specifically target drugs via TfR-mediated endocytosis to cancer cells and will help to pave the way for clinical studies as a potential targeting molecule.

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