Cobalt Ferrite Nanoparticles for Tumor Therapy: Effective Heating versus Possible Toxicity

Magnetic nanoparticles (MNPs) are widely considered for cancer treatment, in particular for magnetic hyperthermia (MHT). Thereby, MNPs are still being optimized for lowest possible toxicity on organisms while the magnetic properties are matched for best heating capabilities. In this study, the biocompatibility of 12 nm cobalt ferrite MNPs, functionalized with citrate ions, in different dosages on mice and rats of both sexes was investigated for 30 days after intraperitoneal injection. The animals’ weight, behavior, and blood cells changes, as well as blood biochemical parameters are correlated to histological examination of organs revealing that cobalt ferrite MNPs do not have toxic effects at concentrations close to those used previously for efficient MHT. Moreover, these MNPs demonstrated high specific loss power (SLP) of about 400 W g−1. Importantly the MNPs retained their magnetic properties inside tumor tissue after intratumoral administration for several MHT cycles within three days. Thus, cobalt ferrite MNPs represent a perspective platform for tumor therapy by MHT due to their ability to provide effective heating without exerting a toxic effect on the organism. This opens up new avenues for smaller MNPs sizes while their heating efficiency is maintained.

Computational Study Regarding CoxFe3−xO4 Ferrite Nanoparticles with Tunable Magnetic Properties in Superparamagnetic Hyperthermia for Effective Alternative Cancer Therapy

The efficacy in superparamagnetic hyperthermia (SPMHT) and its effectiveness in destroying tumors without affecting healthy tissues depend very much on the nanoparticles used. Considering the results previously obtained in SPMHT using magnetite and cobalt ferrite nanoparticles, in this paper we extend our study on CoxFe3−xO4 nanoparticles for x = 0–1 in order to be used in SPMHT due to the multiple benefits in alternative cancer therapy. Due to the possibility of tuning the basic observables/parameters in SPMHT in a wide range of values by changing the concentration of Co2+ ions in the range 0–1, the issue explored by us is a very good strategy for increasing the efficiency and effectiveness of magnetic hyperthermia of tumors and reducing the toxicity levels. In this paper we studied by computational simulation the influence of Co2+ ion concentration in a very wide range of values (x = 0–1) on the specific loss power (Ps) in SPMHT and the nanoparticle diameter (DM) which leads to the maximum specific loss power (PsM). We also determined the maximum specific loss power for the allowable biological limit (PsM)l which doesn’t affect healthy tissues, and how it influences the change in the concentration of Co2+ ions. Based on the results obtained, we established the values for concentrations (x), nanoparticle diameter (DM), amplitude (H) and frequency (f) of the magnetic field for which SPMHT with CoxFe3−xO4 nanoparticles can be applied under optimal conditions within the allowable biological range. The obtained results allow the obtaining a maximum efficacy in alternative and non-invasive tumor therapy for the practical implementation of SPMHT with CoxFe3−xO4 nanoparticles.

Study on Maximum Specific Loss Power in Fe3O4 Nanoparticles Decorated with Biocompatible Gamma-Cyclodextrins for Cancer Therapy with Superparamagnetic Hyperthermia

Different chemical agents are used for the biocompatibility and/or functionality of the nanoparticles used in magnetic hyperthermia to reduce or even eliminate cellular toxicity and to limit the interaction between them (van der Waals and magnetic dipolar interactions), with highly beneficial effects on the efficiency of magnetic hyperthermia in cancer therapy. In this paper we propose an innovative strategy for the biocompatibility of these nanoparticles using gamma-cyclodextrins (γ-CDs) to decorate the surface of magnetite (Fe3O4) nanoparticles. The influence of the biocompatible organic layer of cyclodextrins, from the surface of Fe3O4 ferrimagnetic nanoparticles, on the maximum specific loss power in superparamagnetic hyperthermia, is presented and analyzed in detail in this paper. Furthermore, our study shows the optimum conditions in which the magnetic nanoparticles covered with gamma-cyclodextrin (Fe3O4–γ-CDs) can be utilized in superparamagnetic hyperthermia for an alternative cancer therapy with higher efficiency in destroying tumoral cells and eliminating cellular toxicity.

Radio frequency plasma assisted surface modification of Fe3O4 nanoparticles using polyaniline/polypyrrole for bioimaging and magnetic hyperthermia applications

Surface modification of superparamagnetic Fe3O4 nanoparticles using polymers (polyaniline/polypyrrole) was done by radio frequency (r.f.) plasma polymerization technique and characterized by XRD, TEM, TG/DTA and VSM. Surface-passivated Fe3O4 nanoparticles with polymers were having spherical/rod-shaped structures with superparamagnetic properties. Broad visible photoluminescence emission bands were observed at 445 and 580 nm for polyaniline-coated Fe3O4 and at 488 nm for polypyrrole-coated Fe3O4. These samples exhibit good fluorescence emissions with L929 cellular assay and were non-toxic. Magnetic hyperthermia response of Fe3O4 and polymer (polyaniline/polypyrrole)-coated Fe3O4 was evaluated and all the samples exhibit hyperthermia activity in the range of 42–45 °C. Specific loss power (SLP) values of polyaniline and polypyrrole-coated Fe3O4 nanoparticles (5 and 10 mg/ml) exhibit a controlled heat generation with an increase in the magnetic field.

Theoretical Study on Specific Loss Power and Heating Temperature in CoFe2O4 Nanoparticles as Possible Candidate for Alternative Cancer Therapy by Superparamagnetic Hyperthemia

In this paper, we present a theoretical study on the maximum specific loss power in the admissible biological limit (PsM)l for CoFe2O4 ferrimagnetic nanoparticles, as a possible candidate in alternative and non-invasive cancer therapy by superparamagnetic hyperthermia. The heating time of the nanoparticles (Δto) at the optimum temperature of approx. 43 °C for the efficient destruction of tumor cells in a short period of time, was also studied. We found the maximum specific loss power PsM (as a result of superparamegnetic relaxation in CoFe2O4 nanoparticles) for very small diameters of the nanoparticles (Do), situated in the range of 5.88–6.67 nm, and with the limit frequencies (fl) in the very wide range of values of 83–1000 kHz, respectively. Additionally, the optimal heating temperature (To) of 43 °C was obtained for a very wide range of values of the magnetic field H, of 5–60 kA/m, and the corresponding optimal heating times (Δto) were found in very short time intervals in the range of ~0.3–44 s, depending on the volume packing fraction (ε) of the nanoparticles. The obtained results, as well as the very wide range of values for the amplitude H and the frequency f of the external alternating magnetic field for which superparamagnetic hyperthermia can be obtained, which are great practical benefits in the case of hyperthermia, demonstrate that CoFe2O4 nanoparticles can be successfully used in the therapy of cancer by superaparamagnetic hyperthermia. In addition, the very small size of magnetic nanoparticles (only a few nm) will lead to two major benefits in cancer therapy via superparamagnetic hyperthermia, namely: (i) the possibility of intracellular therapy which is much more effective due to the ability to destroy tumor cells from within and (ii) the reduced cell toxicity.

Magnetic nanoparticles hyperthermia in a non-adiabatic and radiating process

We investigate the magnetic nanoparticles hyperthermia in a non-adiabatic and radiating process through the calorimetric method. Specifically, we propose a theoretical approach to magnetic hyperthermia from a thermodynamic point of view. To test the robustness of the approach, we perform hyperthermia experiments and analyse the thermal behavior of magnetite and magnesium ferrite magnetic nanoparticles dispersed in water submitted to an alternating magnetic field. From our findings, besides estimating the specific loss power value from a non-adiabatic and radiating process, thus enhancing the accuracy in the determination of this quantity, we provide physical meaning to a parameter found in literature that still remained not fully understood, the effective thermal conductance, and bring to light how it can be obtained from experiment. In addition, we show our approach brings a correction to the estimated experimental results for specific loss power and effective thermal conductance, thus demonstrating the importance of the heat loss rate due to the thermal radiation in magnetic hyperthermia.

Publisher Correction: Concentration-dependent oscillation of specific loss power in magnetic nanofluid hyperthermia

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Concentration-dependent oscillation of specific loss power in magnetic nanofluid hyperthermia

Magnetic dipole coupling between the colloidal superparamagnetic nanoparticles (SPNPs) depending on the concentration has been paid significant attention due to its critical role in characterizing the Specific Loss Power (SLP) in magnetic nanofluid hyperthermia (MNFH). However, despite immense efforts, the physical mechanism of concentration-dependent SLP change behavior is still poorly understood and some contradictory results have been recently reported. Here, we first report that the SLP of SPNP MNFH agent shows strong concentration-dependent oscillation behavior. According to the experimentally and theoretically analyzed results, the energy competition among the magnetic dipole interaction energy, magnetic potential energy, and exchange energy, was revealed as the main physical reason for the oscillation behavior. Empirically demonstrated new finding and physically established model on the concentration-dependent SLP oscillation behavior is expected to provide biomedically crucial information in determining the critical dose of an agent for clinically safe and highly efficient MNFH in cancer clinics.