It has been reported that the overexpression of α-casein in some breast cancer cells lines results in apoptosis, re-differentiation, and reduction of cell migration. This was attributed to the activation of the interferon/STAT1 pathway. Based on this information we hypothesized that α-casein can be potentially used as a drug to treat cancer but must be delivered efficiently. We developed a drug delivery system consisting of α-casein nanoparticles coated with chitosan modified with folic acid. It is expected to deliver α-casein to cells overexpressing the folic acid receptor on their surface and release it under acidic condition. In order to determine if α-casein can indeed induce apoptosis when added externally to cells we treated MDA-MB-231, HeLa, and A549 cells with different concentrations of α-casein. Cell viability was assessed using the MTS assay. α-Casein nanoparticles were obtained via a nanoprecipitation method and coated by adding the nanoparticles suspension to a chitosan solution. The impact of this process on the protein structure was studied with circular dichroism. Folic acid modification was performed using the EDC/NHS reaction. Diameter, morphology and charge surface of the nanoparticles were studied with dynamic light scattering, scanning electron microscopy and zeta potential measurement respectively. The cell viability studies showed apoptosis after 24 hours of treatment in MDA-MB-231 and A549 and 48 hours in HeLa cells. We obtained spherical nanoparticles with a diameter of 129 nm and 280 nm before and after coating respectively. No major change on the protein structure was detected. Positive zeta potential values of the coated nanoparticles confirmed the presence of chitosan on the nanoparticles surface. Our results show that α-casein could act as a tumor suppressor when is added externally. We are currently working on more characterization of the drug delivery system and intend to perform viability and confocal studies to test its efficacy.

Study of alpha casein potential as anticancer drug and development of a nano-sized targeted drug delivery system

253rd National Meeting (2017)

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