Targeted Anticancer Therapy: Ovotransferrin as a Selective Carrier for Enhanced Drug Delivery to Cancer Cells

Despite the 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 explores the potential of ovotransferrin (Ovotransferrin ) as a carrier molecule to allow specific targeting of anticancer drugs to cancer cells via the transferrin receptor (TfR). A receptor binding assay proved that Ovotransferrin binds to the transferrin receptor of human colon cancer cells (TfR). Two anticancer drugs, carboplatin (CBP) and paclitaxel (PTX) were non-covalently conjugated with Ovotransferrin 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 efficiently 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 the nuclei as the cell membrane lost its integrity. The red fluorescence was accompanied by chromatin condensation and fragments, indicating apoptosis. The results demonstrate, for the first time, that OTf could target drugs via TfR-mediated endocytosis to cancer cells specifically and will help pave the way for clinical studies as a potential targeting molecule.