The use of nanoferromagnetics to increase the cytotoxic effect of antitumor drugs.
OBJECTIVE
To investigate the influence of ferromagnetic nanoparticles on antitumor effect of doxorubicin and mitochondria oxidative phosphorylation.


METHODS
The study was carried out on the mice-hybrids (C57Bl/6xDBA/2) with intraperitoneally (i/p) transplantated Ehrlich ascitic carcinoma. Single i/p injection of doxorubicin (Dox), stabilized ferromagnetic nanoparticles (Fe3O4; 20-40 nm; FM) or their combination were performed 7 days after tumor transplantation. The cytotoxic effect of agents, morphology and cell cycle of tumor cells were studied 24, 48 and 72 h after Dox administration.


RESULTS
The investigations showed that ferromagnetic nanoparticles increased the cytotoxic effect of doxorubicin on Ehrlich ascsmall i, Ukrainiantic carcinoma mainly 48 h after agents' administration. The largest number of apoptotic cells was observed in group of animals in which doxorubicin was administered before ferromagnetic nanoparticles. Moreover, the ferromagnetic nanoparticles at concentration 1.45 microg Fe/ml and, particularly, 7.25 microg Fe/ml decreased mitochondria oxygen consumption in phosphorylation state that may negatively influence their living capability.


CONCLUSIONS
Obtained data point out the perspective of use of certain sized FM nanoparticles to increase the cytotoixc effect of antitumor drugs.
R. E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, NAS of Ukraine, Kiev, Ukraine. todor_igor@yahoo.com
V F
VF
Chekhun
I N
IN
Todor
N Yu
NY
Lukyanova
S I
SI
Shpyleva
L A
LA
Naleskina
I K
IK
Khaetsky
G I
GI
Kulik
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects*; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy / Q000473:pathology*; D002453:Cell Cycle / Q000187:drug effects*; D004317:Doxorubicin / Q000633:toxicity*; D004357:Drug Synergism; D005290:Ferric Compounds / Q000494:pharmacology*; D053768:Metal Nanoparticles; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D010101:Oxygen Consumption
D000903:Antibiotics, Antineoplastic; D005290:Ferric Compounds; C001215:ferrite; D004317:Doxorubicin