Effect of Iron Oxide Nanoparticle Shape on Doxorubicin Drug Delivery Toward LNCaP and PC-3 Cell Lines
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In this paper, we investigated the delivery efficiency of doxorubicin by magnetite nanoparticles with different shape to LNCaP and PC-3 prostate cancer cell lines. Cubic and spherical nanoparticles of magnetite were synthesized in organic medium and hydrophilized by non-ionic surfactant Pluronic F127—polyethylene-polypropylene oxide polymer. Doxorubicin was loaded into hydrophobic region of polymeric shell. We have observed that cytotoxicity and distribution of doxorubicin in cells changed significantly in case of drug loaded into nanoparticles in comparison with free doxorubicin. We have shown that this change is due to two main reasons: (1) slower internalization of nanoparticles by cells compared to free doxorubicin and (2) slow and incomplete release of doxorubicin from nanoparticle polymer shell. Interestingly, nanoparticle shape influenced cytotoxicity and the dynamics of drug accumulation inside cancer cells. We have found that doxorubicin-loaded cubic nanoparticles were more toxic for both cell lines compared to spherical ones. Moreover, doxorubicin from cubic nanoparticles accumulated in cells faster than the drug loaded in spherical nanoparticles. So, our work shows that for efficient drug delivery, not only size and coating should be taken into account but also the shape of initial core as it plays an important role in nanoparticle interaction with cells.
KeywordsIron oxide nanoparticles Nanoparticle shape Drug delivery Doxorubicin Human prostate cancer cell lines
The authors thank the Program of Moscow State University Development (PNR 5.13) for assistance in the study of nanoparticle intracellular localization by JEM-1400 (JEOL) transmission electron microscope.
A.G.M. conceived the research and guided the project. T.R.N. synthesized, modified, and characterized nanoparticles. G.I.S. carried out XRD and magnetic measurements. A.S.G. conducted the biological experiments. O.A.Z. prepared ultrathin sections for transmission electron microscopy analysis. T.R.N., A.S.G., M.A.A., A.G.S., and A.G.M. discussed the results. T.R.N. and A.S.G. wrote the manuscript. O.S.S., M.A.A., I.B.A., I.I.K., A.G.M., and A.G.S. critically revised the manuscript. All authors approved the final version of the manuscript.
The work was supported by the Ministry of Education and Science of the Russian Federation (grant no. 14.578.21.0201 (RFMEFI57816X0201)).
Compliance with Ethical Standards
The authors declare that they have no competing interests.
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