Chitosan-coated bovine serum albumin nanocarriers mediate efficient delivery of methotrexate in breast cancer therapeutics

Methotrexate (MTX) is highly investigated for the treatment of various malignancies, including breast cancer. However, its use is limited because of its drawbacks related to high toxicity, poor solubility, and permeability as well as short plasma half-life. Therefore, in this study, we suggested MTX-loaded novel protein and polysaccharide-based nanovehicles in order to enhance the effect of MTX for breast cancer treatment. We pre-pared MTX-loaded uncoated and chitosan-coated bovine serum albumin (BSA) nanoparticles and characterized by particle size and distribution, surface charge, encapsulation efficiency and morphological structure. Furthermore, we compared the cellular uptake, cytotoxic effect and apoptosis induction properties of free MTX, MTX-loaded uncoated and chitosan-coated BSA nanoparticles on MCF-7 breast cancer cells. The chitosan-coating turned the surface charge of the uncoated BSA nanoparticles from -25.5 mV up to 53.3 mV and the cellular uptake performances of nanoparticles were significantly changed according to the surface charge of nanoparticles. The positively charged chitosan-coated nanoparticles were more efficiently internalized than negatively charged uncoated BSA nanoparticles. Besides, in line with cellular uptake experiments, the cytotoxic effect as well as apoptosis induction properties of chitosan-coated BSA nanoparticles were found to be greater than both uncoated BSA nanoparticles and free MTX. The analyses showed that the MCF7 cell viability was decreased to 58 and 35% at the end of 48-h treatment at 5 mu g mL(-1) dose MTX by uncoated and coated BSA nanoparticles, respectively. Moreover, chitosan-coated BSA nanoparticles lead to 3.67- and 2.23-folds higher apoptosis-related cellular death than that of free drug and uncoated nanoparticles, respectively. Based on our findings, the designed MTX-loaded chitosan-coated BSA nanoparticles can be suggested as a novel and efficient strategy for the treatment of breast cancer.