Abstract B111: Targeted tumor therapy with doxorubicin bound to iron oxide nanoparticles and alleviation of drug toxicity

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Abstract B111 Introduction Doxorubicin is an anthracycline antibiotic with potent anticancer activity used widely against human neoplasms including a variety of solid tumors like head and neck tumors, breast cancer, bladder and testicular cancer, small cell lung cancer. It is also effective in acute lymphoblastic and non- lymphoblastic leukemias and malignant lymphomas. But its irreversible toxic effect, dose related cardiomyopathy, significantly limits its therapeutic use. Complexing of Doxorubicin with magnetic nanoparticles may help to selectively target tumor tissue, while lowering its concentration in the circulation, thus reducing its toxic effects. In the present study the effect of iron oxide magnetic nanoparticles (Fe3O4 nanoparticles with PVP coating) complexed with Doxorubicin (Doxo) in DLA cells and murine solid tumour was evaluated. The antitumour effect of the complex with an externally applied magnetic field to target the complex to the tumour site after oral administration was also studied. Materials and Methods Fe3O4-PVP nanoparticles were coated with poly oxy ethylene 25 propylene glycol stearate (POES) and then complexed with doxorubicin to obtain Fe3O4-PVP-POES-Doxo nanoparticles. The drug binding was ensured by checking the absorption spectra of the solutions. Male Swiss albino mice bearing transplanted DLA solid tumor on hind legs were administered with the drug and nanoparticle complex, orally and treated with a magnet on the tumour for 15 min for 7 days. The hind leg thicknesses were measured using a vernier caliper once in three days and the tumor volume was calculated. Results In animals given Fe3O4-PVP-POES-Doxo and treated with magnet, there was a visible reduction of tumor growth, during the treatment period and there was no reappearance of tumour in this group after the treatment duration, whereas animals treated with Doxo, Fe3O4-PVP-POES, Fe3O4-PVP-POES-Doxo without magnet exposure showed a comparable reduction in tumour growth during the treatment period but later the tumor showed a logarithmic growth.. Fe3 O4 - PVP POES- Doxorubicin complex showed more cytotoxicity on DLA cells compared to Fe3 O4 - PVP or Doxorubicin alone. Treatment of DLA cells with the nanoparticle-doxorubicin complex resulted in higher apoptotic index than that of treatment with doxorubicin or nanoparticles alone. In the heart tissue of tumour bearing mice treated with Fe3 O4 - PVP-POES- Doxorubicin without magnetic field application there was decrease in levels of GSH and increase in the levels peroxides of lipids ( monitored as TBARS) due to the oxidative stress induced by the drug in heart tissue while in the animals subjected to the applicatiotion of magnetic field following Fe3 O4 - PVP-POES-Doxorubicin treatment the levels were similar to the control animals suggesting alleviation of cardiotoxicity due to magnetic targeting. Conclusions: Magnet mediated targeting could result in increase of the concentration of the drug nanoparticle complex at the tumor site and reduce the circulating levels of the drug complex. Further studies are needed to translate this finding from bench to bed side. Citation Information: Cancer Prev Res 2008;1(7 Suppl):B111.