Application of C60 Fullerene-Doxorubicin Complex for Tumor Cell Treatment In Vitro and In Vivo.

Abstract

Development of nanocarriers for effective drug delivery to molecular targets in tumor cells is a real problem in modern pharmaceutical chemistry. In the present work we used pristine C60 fullerene as a platform for delivery of anticancer drug doxorubicin (Dox) to its biological targets. The formation of a complex of C60 fullerene with Dox (C60 + Dox) is described and physico-chemical characteristics of such complex are presented. It was found that Dox conjugation with C60 fullerene leads to 1.5-2-fold increase in Dox toxicity towards various human tumor cell lines, compared with such effect when the drug is used alone. Cytotoxic activity of C60 + Dox complex is accompanied by an increased level of cell produced hydrogen peroxide at early time point (3 h) after its addition to cultured cells. At the same time, cellular production of superoxide radicals does not change in comparison with the effect of Dox alone. Cytomorphological studies have demonstrated that C60 + Dox complexes kill tumor cells by apoptosis induction. The results of in vivo experiments using Lewis lung carcinoma in mice confirmed the enhancement of the Dox toxicity towards tumor cells after drug complexation with C60 fullerene. The effect of such complex towards tumor-bearing mice was even more pronounced than that in the in vitro experiment with targeting human tumor cells. The tumor volume decreased by 2.5 times compared with the control, and an average life span of treated animals increased by 63% compared with control. The obtained results suggest a great perspective of application of C60 + Dox complexes for chemotherapy of malignant tumors.

• Authors: R R Panchuk, S V Prylutska, V V Chumakl, N R Skorokhyd, L V Lehka, M P Evstigneev, Yu I Prylutskyy, W Berger, P Heffeter, P Scharff, U Ritter, R S Stoika
• Journal: Journal of biomedical nanotechnology (J Biomed Nanotechnol) Vol. 11 Issue 7 Pg. 1139-52 (Jul 2015) ISSN: 1550-7033 [Print] United States
• PMID: 26307837 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Fullerenes
• Nanoconjugates
• Doxorubicin
• fullerene C60

Topics

• Animals
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage)
• Apoptosis (drug effects)
• Cell Survival (drug effects)
• Doxorubicin (administration & dosage)
• Fullerenes (administration & dosage, chemistry)
• HL-60 Cells
• Humans
• MCF-7 Cells
• Male
• Mice
• Mice, Inbred C57BL
• Nanoconjugates (administration & dosage, chemistry, ultrastructure)
• Neoplasms, Experimental (drug therapy, pathology)
• Particle Size
• Treatment Outcome