324
V. Orel et al.
proposed. However, this type of therapy requires a sufficient tumor area to be
covered by the NPs for successful treatment. But this can be difficult to achieve
in real clinical practice. Also, hematogenous dissemination of metastatic tumors is
also the one of the challenges for treatment by magnetic NPs [4, 5].
In order to overcome the above issues, we have proposed the magnetic resonance
nanotherapy with magneto-mechano-chemically synthesized AMNC that have a
magnetic memory effect. In our previous studies [6], it was shown that the treatment
by AMNC consisted of iron oxide Fe 3 O 4 NPs and antitumor drug doxorubicin
(DOXO) with simultaneous electromagnetic radiation using the magnetic resonance
effect during moderate hyperthermia of Lewis lung carcinoma had the highest
antitumor effect compared to the conventional DOXO or AMNC without electromagnetic radiation. This opens new prospects for development of personalized
and individually optimized nanotechnology-based treatment protocols to be implemented in clinics for cancer patients at higher risks of tumor dissemination.
Furthermore, personalized synthesis of AMNC with manageable magnetic properties is a key component in the nanotechnology approach. It was earlier shown
that the radio-frequency electromagnetic radiation in shortwave range and constant
magnetic fields impact on magnetic memory (the magnetic properties) of magnetomechano-chemically synthesized AMNC [7, 8].
In view of the previously found correlation between mechanical stress and
magnetic properties in nanometer Fe films [9], this paper sheds new light on understanding the nonlinear interactions of mechanical and electromagnetic phenomena
in AMNC. Therefore, we have studied the influence of mechanical vibration and
electromagnetic irradiation on the AMNC magnetic properties during magnetomechano-chemical synthesis.
20.2 Materials and Methods
20.2.1 Magneto-Mechano-Chemical Synthesis
Fe 3 O 4 NPs (International Center for Electron Beam Technologies of E.O. Paton
Electric Welding Institute, Ukraine) with diameters in the range of 20–40 nm and
DOXO (Actavis, Romania) were processed in a high-precision magneto-mechanical
milling chamber (NCI, Ukraine), which was designed according to a typical
scheme for the magnetic resonance apparatus. The samples of Fe 3 O 4 and DOXO
were placed in the diamagnetic chamber together with metallic balls. Mechanical
processing was performed by vertical vibrations of the chamber at frequencies 15,
20, 25, 30, and 35 Hz and an amplitude of 9 mm for 5 min. Simultaneously, ER
with frequency 42 MHz and output power of 2 W for 5 min in combination with
constant magnetic field with induction 8 mT was applied. In addition, we have
investigated the magnetic properties of magneto-mechano-chemically activated iron
oxide NPs (without DOXO), mechano-chemically synthesized AMNC without
electromagnetic radiation, and a mixture of DOXO and Fe 3 O 4 NPs without any
influence.
V. Orel et al.
proposed. However, this type of therapy requires a sufficient tumor area to be
covered by the NPs for successful treatment. But this can be difficult to achieve
in real clinical practice. Also, hematogenous dissemination of metastatic tumors is
also the one of the challenges for treatment by magnetic NPs [4, 5].
In order to overcome the above issues, we have proposed the magnetic resonance
nanotherapy with magneto-mechano-chemically synthesized AMNC that have a
magnetic memory effect. In our previous studies [6], it was shown that the treatment
by AMNC consisted of iron oxide Fe 3 O 4 NPs and antitumor drug doxorubicin
(DOXO) with simultaneous electromagnetic radiation using the magnetic resonance
effect during moderate hyperthermia of Lewis lung carcinoma had the highest
antitumor effect compared to the conventional DOXO or AMNC without electromagnetic radiation. This opens new prospects for development of personalized
and individually optimized nanotechnology-based treatment protocols to be implemented in clinics for cancer patients at higher risks of tumor dissemination.
Furthermore, personalized synthesis of AMNC with manageable magnetic properties is a key component in the nanotechnology approach. It was earlier shown
that the radio-frequency electromagnetic radiation in shortwave range and constant
magnetic fields impact on magnetic memory (the magnetic properties) of magnetomechano-chemically synthesized AMNC [7, 8].
In view of the previously found correlation between mechanical stress and
magnetic properties in nanometer Fe films [9], this paper sheds new light on understanding the nonlinear interactions of mechanical and electromagnetic phenomena
in AMNC. Therefore, we have studied the influence of mechanical vibration and
electromagnetic irradiation on the AMNC magnetic properties during magnetomechano-chemical synthesis.
20.2 Materials and Methods
20.2.1 Magneto-Mechano-Chemical Synthesis
Fe 3 O 4 NPs (International Center for Electron Beam Technologies of E.O. Paton
Electric Welding Institute, Ukraine) with diameters in the range of 20–40 nm and
DOXO (Actavis, Romania) were processed in a high-precision magneto-mechanical
milling chamber (NCI, Ukraine), which was designed according to a typical
scheme for the magnetic resonance apparatus. The samples of Fe 3 O 4 and DOXO
were placed in the diamagnetic chamber together with metallic balls. Mechanical
processing was performed by vertical vibrations of the chamber at frequencies 15,
20, 25, 30, and 35 Hz and an amplitude of 9 mm for 5 min. Simultaneously, ER
with frequency 42 MHz and output power of 2 W for 5 min in combination with
constant magnetic field with induction 8 mT was applied. In addition, we have
investigated the magnetic properties of magneto-mechano-chemically activated iron
oxide NPs (without DOXO), mechano-chemically synthesized AMNC without
electromagnetic radiation, and a mixture of DOXO and Fe 3 O 4 NPs without any
influence.