Abstract
PURPOSE: Breast cancer is one of the most lethal types of cancer in women. Curcumin showed therapeutic potential against breast cancer, but applying that by itself does not lead to the associated health benefits due to its poor bioavailability, which appears to be primarily due to poor absorption, rapid metabolism, and rapid elimination. Moreover, poor water solubility of curcumin causes accumulation of a high concentration of curcumin and so decrease its permeability to the cell. Many strategies are employed to reduce curcumin metabolism such as adjuvants and designing novel delivery systems. Therefore, in this study sodium alginate and chitosan were used to synthesize the hydrogels that are known as biocompatible, hydrophilic and low toxic drug delivery systems. Also, folic acid was used to link to chitosan in order to actively targetfolate receptors on the cells. METHODS: Chitosan-β-cyclodextrin-TPP-Folic acid/alginate nanoparticles were synthesized and then curcumin was loaded on them. Interaction between the constituents of the particles was characterized by FTIR spectroscopy. Morphological structures of samples were studied by FE-SEM. Release profile of curcumin was determined by dialysis membrane. The cytotoxic test was done on the Kerman male breast cancer (KMBC-10) cell line by using MTT assay. The viability of cells was detected by fluorescent staining. Gene expression was investigated by real-time PCR. RESULTS: The encapsulation of curcumin into nano-particles showed an almost spherical shape and an average particle size of 155 nm. In vitro cytotoxicity investigation was indicated as dose-respond reaction against cancer breast cells after 24 h incubation. On the other hand, in vitro cell uptake study revealed active targeting of CUR-NPs into spheroids. Besides, CXCR (4) expression was detected about 30-fold less than curcumin alone. The CUR-NPs inhibited proliferation and increased apoptosis in spheroid human breast cancer cells. CONCLUSION: Our results showed the potential of NPs as an effective candidate for curcumin delivery to the target tumor spheroids that confirmed the creatable role of folate receptors.