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Vol 47(2013) N 5 p. 743-750;
V.I. Popenko*, O.G. Leonova, V.I. Salyanov, N.N. Orlova, P.V. Spirin, V.S. Prasolov, Y.M. Evdokimov

Dynamics of Penetration of Rigid Nanostructures of Double-Stranded DNA Complexed with Gadolinium into CHO Cells

Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991 Russia

*popenko@eimb.ru
Received - 2012-12-21; Accepted - 2013-04-28

Currently, neutron capture therapy is a promising cancer treatment. This method is based on the reaction of thermal neutron capture by some nonradioactive elements (e.g., Gd157), which results in the subsequent emission of electrons and gamma rays. An effective instrument for delivering gadolinium into tumor tissue are "rigid" nanostructures (NSs) based on double-stranded DNA complexes with gadolinium (NS-Gd). The local concentration of Gd in these nanostructures may reach 40%. To optimize the process of neutron capture therapy, it is very important to investigate possible mechanisms of the penetration of NS-Gd particles into tumor cells. In this work, the dynamics of interaction between NS-Gd and cultivated Chinese hamster ovary cells (CHO) was studied by confocal and electron microscopy. NS-Gd were shown to be able to enter CHO cells. This process started after about 1 h of incubation. After 6 h, NS-Gd particles were detected in almost all cells. A further increase in the incubation time did not lead to significant changes in cell morphology, although the amount of NS-Gd inside cells continued to increase. The plasma membranes of the cells remained intact. Once entering the cells, NS-Gd particles remained there for a long time. The data show that NS-Gd has relatively low toxicity and suggest that the presence of NS-Gd in tumor cells does not prevent their division. The data are important for improving the efficiency of the method of neutron-capture therapy.

neutron-capture therapy, dsDNA-based nanostructures, confocal microscopy, electron microscopy



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