STUDY OF THE COMBINED EFFECT OF DOXORUBICIN-LOADED SUPERPARAMAGNETIC NANOPARTICLES AND NON-IONISING ELECTROMAGNETIC IRRADIATION ON WALKER-256 CARCINOSARCOMA.

OBJECTIVE

to examine the combined effect of doxorubicinloaded superparamagnetic nanoparticles and nonionising electromagnetic irradiation on Walker256 carcinosarcoma using magnetochemical technology.

MATERIALS AND

METHODS

Noninbred female rats were divided into the control (untreated tumourbearing) andexperimental group receiving superparamagnetic Fe3O4 nanoparticles (3 mg/kg, SigmaAldrich, USA) loaded withdoxorubicin (1.5 mg/kg, Pfizer, Italy) and exposed to a static magnetic (30 mT) and electromagnetic field (42 MHz)for 15 minutes (5 sessions from day 2 after tumour inoculation). Tumour structural changes were evaluated usingmagnetic resonance imaging at 1.5 T field strength and 63.9 MHz frequency (Intera, Philips, Netherlands), followedby texture heterogeneity analysis with LifeX software (France). Free iron, ceruloplasmin, superoxide radical andnitric oxide were measured by electron paramagnetic resonance spectroscopy to characterise the tumour and bloodredox state.

RESULTS

Combined treatment reduced tumour volume by 44-64 % on days 13-18 compared with the control (p < 0.05).Texture parameters (intensity, entropy, dissimilarity, autocorrelation, cluster tendency) in tumour regions of interest on T2 weighted images were 17-53 % lower than in the control (p < 0.05). After treatment, electron paramagnetic resonance spectroscopy revealed lower superoxide radical (4.5fold) and nitric oxide (1.2fold) levels intumour samples, in addition to increased free iron, ceruloplasmin (by 11 %) and reduced superoxide (by 54 %), nitricoxide (by 26 %) in blood samples of tumourbearing animals, compared with the control (p < 0.05).

CONCLUSION

Doxorubicinloaded superparamagnetic nanoparticles combined with electromagnetic irradiationinhibit Walker256 carcinosarcoma growth, reduce intratumour heterogeneity and initiate changes in the tumourand blood redox state.