Magnetic properties and antitumor effect of nanocomplexes of iron oxide and doxorubicin

We present a technology and magneto-mechanical milling chamber for the magneto-mechano-chemical synthesis (MMCS) of magneto-sensitive complex nanoparticles (MNC) comprising nanoparticles Fe3O4 and anticancer drug doxorubicin (DOXO). Magnetic properties of MNC were studied with vibrating magnetometer and electron paramagnetic resonance. Under the influence of mechano-chemical and MMCS, the complex show a hysteresis curve, which is typical for soft ferromagnetic materials. We also demonstrate that Lewis lung carcinoma had a hysteresis loop typical for a weak soft ferromagnet in contrast to surrounding tissues, which were diamagnetic. Combined action of constant magnetic field and radio frequency moderate inductive hyperthermia (RFH) below 40 °C and MNC was found to induce greater antitumor and antimetastatic effects as compared to conventional DOXO. Radiospectroscopy shows minimal activity of FeS-protein electron transport chain of mitochondria, and an increase in the content of non-heme iron complexes with nitric oxide in the tumor tissues under the influence of RFH and MNC.From the Clinical EditorThis study reports on the top-down synthesis of magneto-sensitive complex nanoparticles comprised of Fe3O4 nanoparticles and doxorubicin. Authors also found that Lewis lung carcinoma had a hysteresis loop typical for a weak soft ferromagnet in contrast to surrounding tissues, which were diamagnetic. Combined action of constant magnetic field and radio frequency induced moderate hyperthermia induced both antitumor and antimetastatic effects greater than conventional DOX alone.

Graphical AbstractThe magneto-mechano-chemical synthesis (1) is accompanied by splitting of electron energy levels (SEELs) and electron transfer in magnetic field (2) from nanoparticles Fe3O4 to doxorubicin. The concentration of paramagnetic centers (free radicals) is increased in the magneto-sensitive complex (MNC) (3). The local combined action of constant magnetic and electromagnetic fields and MNC in Lewis lung carcinoma (4) initiated SEELs, free radicals, leading to oxidative stress and electron transport deregulation in the mitochondrion (5). Magnetic nanotherapy more effectively inhibited the synthesis of ATP in mitochondria of tumor cell and induced the death of tumor cells as compared to conventional doxorubicin.Figure optionsDownload high-quality image (414 K)Download as PowerPoint slide