ORIGINAL RESEARCH
The use of iron oxide magnetic nanospheres and nanocubes for targeted doxorubicin delivery into 4t1 mouse breast carcinoma cells
1 Laboratory of Biomedical Nanomaterials National University of Science and Technology MISiS, Moscow
2 Research Laboratory of Tissue-Specific Ligands, Faculty of Chemistry, Lomonosov Moscow State University, Moscow
3 Department of physical materials science, National University of Science and Technology MISiS, Moscow
Correspondеnce should be adressed: Timur R. Nizamov
Leninsky 4, Moscow, 119049; moc.liamg@rumit.vomazin
Funding: the study was supported by the Ministry of Education and Science of the Russian Federation in the context of the Agreement #14.578.21.0201 (project code RFMEFI57816X0201).
Magnetic nanoparticles (MNP) are attracting increasing attention as promising materials for the treatment and diagnosis of cancer. The aim of this work was to explore the effect of the magnetic core shape of iron oxide nanoparticles (NP) on the efficiency of doxorubicin delivery into 4T1 cells. Nanospheres (NS) and nanocubes (NC) were synthesized by thermal decomposition of iron (III) oleate. This method of synthesis enables control over the NP shape and size. The NP were hydrophilized using Pluronic F-127. The obtained particles were doped with doxorubicin in a sodium phosphate buffer. The weight fractions of doxorubicin in the NS and NC were 15.22% and 15.44%, respectively. The IC50 of free doxorubicin was 1 μM. The IC50 of doxorubicin-loaded NS and NC were 6.4 μM and 5.5 μM, respectively. Unloaded NP did not exhibit any toxicity towards the cells at a studied range of concentrations between 1.77 mg/l and 227.2 mg/l. Free doxorubicin demonstrated more vigorous accumulation dynamics in 4T1 cells with a tendency to localize in the cell nucleus, whereas doxorubicin loaded onto iron oxide NP was mainly accumulated in the vesicles surrounding the nucleus and was able to enter it only after being incubated with the cells for 2 h. We conclude that doxorubicin loaded onto cubic-shaped NP is delivered into the cell nucleus a little bit more efficiently at early incubation stages in comparison with nanospheres, but the difference is insignificant.
Keywords: cytotoxicity, iron oxide nanoparticles, nanoparticles shape, drug delivery, doxorubicin