Analysis of toxicity and anticancer activity of micelles of sodium alginate-curcumin

Abstract

Alicja Karabasz1, Dorota Lachowicz2, Anna Karewicz3, Renata Mezyk-Kopec1, Krystyna Stalińska1, Ewa Werner4,5, Agnieszka Cierniak6, Grzegorz Dyduch7, Joanna Bereta1, Monika Bzowska1 1Department of Cell Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Kraków, Poland; 2Academic Centre for Materials and Nanotechnology, AGH University of Science and Technology, Kraków, Poland; 3Faculty of Chemistry, Jagiellonian University, Kraków, Poland; 4Department of Medical Biotechnology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Kraków, Poland; 5Department of Animal Reproduction and Anatomy, Faculty of Animal Science, University of Agriculture, Krakow, Poland; 6Department of General Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Kraków, Poland; 7Department of Pathomorphology, Jagiellonian University Medical College, Kraków, PolandCorrespondence: Monika BzowskaJagiellonian University in Kraków, Faculty of Biochemistry, Biophysics and Biotechnology, Department of Cell Biochemistry, 7 Gronostajowa St., Kraków 30-387, PolandTel [phone]Fax [phone]Email [email protected]: Curcumin is a natural polyphenol with anti-inflammatory, chemopreventive and anticancer activity. However, its high hydrophobicity and poor bioavailability limit its medical application. The development of nanocarriers for curcumin delivery is an attractive approach to overcome its low bioavailability and fast metabolism in the liver. We synthesized a blood compatible alginate-curcumin conjugate, AA-Cur, which formed colloidally stable micelles of approximately 200 nm and, as previously shown, exerted strong cytotoxicity against mouse cancer cell lines. Here we analyze in vivo toxicity and antitumor activity of AA-Cur in two different mouse tumor models.Method: Potential toxicity of intravenously injected AA-Cur was evaluated by: i) analyses of blood parameters (morphology and biochemistry), ii) histology, iii) DNA integrity (comet assay), and iv) cytokine profiling (flow cytometry). Antitumor activity of AA-Cur was evaluated by measuring the growth of subcutaneously inoculated colon MC38-CEA- or orthotopically injected breast 4T1 tumor cells in control mice vs mice treated with AA-Cur.Results: Injections of four doses of AA-Cur did not reveal any toxicity of the conjugate, thus indicating the safety of its use. AA-Cur elicited moderate anti-tumor activity toward colon MC38-CEA or breast 4T1 carcinomas.Conclusion: The tested conjugate of alginate and curcumin, AA-Cur, is non-toxic and safe, but exhibits limited anticancer activity.Keywords: curcumin, alginate conjugates, in vivo toxicity, antitumor activity

Keywords

• curcumin
• alginate conjugates
• in vivo toxicity
• antitumor activity