Nanobiotechnology for health-care
Antitumor efficiency of the natural alkaloids complexed with 
C60 fullerene in Lewis lung carcinoma in vitro and in vivo

D. Rumyantsev1, O. Grabovskiy2, I. Krysiuk2, T. Skaterna2, I. Horak2, 
L. Drobot2, D. Franskevych3, O. Matyshevska2, S. Prylutska3, A. Senenko1, 
Yu. Prylutskyy3, U. Ritter4 

1Institute of Physics of NAS of Ukraine, Nauki Av., 46, 03028 Kyiv, Ukraine.
E-mail:prylut@ukr.net 
2Palladin Institute of Biochemistry, NAS of Ukraine, 9 Leontovicha Str., 01030 Kyiv, Ukraine.
3Taras Shevchenko National University of Kyiv, Volodymyrska Str., 64, 01601 Kyiv, Ukraine.
4Technical University of Ilmenau, Institute of Chemistry and Biotechnology, Weimarer Str., 25, 98693 Ilmenau, Germany.

Medicines with small molecule sizes have unique advantages for medical usage due to non-immunogenic effect, variety of administration ways, simple absorption and preparation. Piperlongumine (PL) and homoharringtonine (HHT) - plant compounds, which are widely used in Chinese traditional medicine, have multiple pharmacological properties and exhibit antitumor effect [1]. However, their use is limited due to the low stability and bioavailability, as well as the need for use in high, toxic doses [2]. The use of nanosize systems for the efficient delivery of natural alkaloids to tumor cells can help to solve this problem and increase their therapeutic efficacy [3]. In this study, the natural alkaloids (PL and HHT), noncovalently bound to a carbon nanostructure C60 fullerene (C60) at various molar ratios of the components, is explored against Lewis lung carcinoma (LLC). Water-soluble C60-PL/HHT nanocomplexes were characterized by the probe microscopic and spectroscopic techniques. PL/HHT release from C60-PL/HHT nanocomplexes is promoted with medium acidification. LLC cells treatment with C60-PL/HHT nanocomplexes is followed by enhanced PL/HHT intracellular uptake as compared to free PL/HHT. The cytotoxicity of the studied agents follows the order: free PL/HHT<C60-PL/HHT nanocomplex. C60-PL/HHT nanocomplexes induce caspase 3/7 activation and suppress the migration activity of LLC cells. The therapeutic potency of C60-PL/HHT nanocomplexes is confirmed in a mouse model of LLC. This study indicates that сomplexation of natural alkaloids with C60 may be a novel therapeutic strategy against lung carcinoma. This research was supported by the National Research Foundation of Ukraine (project 2020.02/0060).
 
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