Eliyahu Drori, Valeria Rahamim, Dhaval Patel, Yamm Anker, Sivan Meir, Gal Uzan, Chen Drori, Yaakov Anker, Aharon Azagury Department of Chemical Engineering, Ariel University, Ariel, IsraelCorrespondence: Aharon Azagury, Email [email protected]: Cancer treatment often involves significant side effects, necessitating the need for more selective therapies. Spirulina-derived nanoparticles (sNPs) have shown promise as a targeted anticancer strategy.Methods: This study evaluated the cytotoxic effects of sNPs on cancer cell lines TR-146 (buccal), Caco-2 and HT-29 (colorectal), and MCF-7 (breast), compared to the non-cancerous MCF-10A cells. Cytotoxicity was assessed using the XTT assay at concentrations of 25– 500 mg/mL over 3– 48 hours. Cellular uptake was quantified via fluorescence-activated cell sorting (FACS) and fluorescence microscopy, and endocytic inhibitors were used to investigate the uptake mechanism.Results: sNPs induced 30– 80% mortality in cancer cells, while non-cancerous MCF-10A cells exhibited negligible mortality (< 5%). Male-derived Caco-2 cells were more sensitive to sNPs than female-derived HT-29 cells, suggesting potential sex-based differences. FACS analysis showed 100% cellular uptake in all cancer cells, with TR-146 exhibiting the highest fluorescence intensity. Endocytosis inhibition studies revealed that caveolae-mediated endocytosis played a significant role in sNP uptake, particularly in TR-146 and Caco-2 cells.Discussion: These findings demonstrate the potential of sNPs as selective and potent anticancer agents, warranting further research to optimize their clinical application. Keywords: Spirulina, nanoparticles, cancer therapy, biomimetics, cellular uptake, endocytic inhibitor
