The Selective in vitro Cytotoxicity of Spirulina-Derived Nanoparticles: A Novel Biomimetic Approach to Cancer Therapy

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 inhibitors