Magnetite nanorods (MNRs) are synthesized based on the use of hematite nanoparticles of the desired geometry and dimensions as templates. The nanorods are shown to be highly monodisperse, with a 5:1 axial ratio, and with a 275 nm long semiaxis. The MNRs are intended to be employed as magnetic hyperthermia and photothermia agents, and as drug vehicles. To achieve a better control of their photothermia response, the particles are coated with a layer of gold, after applying a branched polyethyleneimine (PEI, 2 kDa molecular weight) shell. Magnetic hyperthermia is performed by application of alternating magnetic fields with frequencies in the range 118–210 kHz and amplitudes up to 22 kA/m. Photothermia is carried out by subjecting the particles to a near-infrared (850 nm) laser, and three monochromatic lasers in the visible spectrum with wavelengths 480 nm, 505 nm, and 638 nm. Best results are obtained with the 505 nm laser, because of the proximity between this wavelength and that of the plasmon resonance. A so-called dual therapy is also tested, and the heating of the samples is found to be faster than with either method separately, so the strengths of the individual fields can be reduced. Due to toxicity concerns with PEI coatings, viability of human hepatoblastoma HepG2 cells was tested after contact with nanorod suspensions up to 500 µg/mL in concentration. It was found that the cell viability was indistinguishable from control systems, so the particles can be considered non-cytotoxic in vitro. Finally, the release of the antitumor drug doxorubicin is investigated for the first time in the presence of the two external fields, and of their combination, with a clear improvement in the rate of drug release in the latter case.
Among the strategies employed to overcome the development of multidrug-resistant bacteria, directed chemotherapy combined with local therapies (e.g., magnetic hyperthermia) has gained great interest. A nano-assembly coupling the antimicrobial peptide AS-48 to biomimetic magnetic nanoparticles (AS-48-BMNPs) was demonstrated to have potent bactericidal effects on both Gram-positive and Gram-negative bacteria when the antimicrobial activity of the peptide was combined with magnetic hyperthermia. Nevertheless, intracellular pathogens remain challenging due to the difficulty of the drug reaching the bacterium. Thus, improving the cellular uptake of the nanocarrier is crucial for the success of the treatment. In the present study, we demonstrate the embedding cellular uptake of the original nano-assembly into THP-1, reducing the toxicity of AS-48 toward healthy THP-1 cells. We optimized the design of PLGA[AS-48-BMNPs] in terms of size, colloidal stability, and hyperthermia activity (either magnetic or photothermal). The stability of the nano-formulation at physiological pH values was evaluated by studying the AS-48 release at this pH value. The influence of pH and hyperthermia on the AS-48 release from the nano-formulation was also studied. These results show a slower AS-48 release from PLGA[AS-48-BMNPs] compared to previous nano-formulations, which could make this new nano-formulation suitable for longer extended treatments of intracellular pathogens. PLGA[AS-48-BMNPs] are internalized in THP-1 cells where AS-48 is liberated slowly, which may be useful to treat diseases and prevent infection caused by intracellular pathogens. The treatment will be more efficient combined with hyperthermia or photothermia.
7 November 2023 in Journal of Magnetism and Magnetic Materials
Local hyperthermia is gaining considerable interest due to its promising antitumor effects. In this context, dual magneto-photothermal cancer therapy holds great promise. For this purpose, the use of nanomaterials has been proposed. Therefore, the aim of this research is to develop a dual magneto-photothermal agent consisting of polydopamine-coated nonspherical magnetic nanoclusters. The physicochemical characterization of the nanoclusters was performed by electron microscopy, electron dispersive X-ray, dynamic light scattering, electrophoretic mobility, thermogravimetric analysis, and Fourier transform infrared spectroscopy. The biocompatibility of the nanoclusters was evaluated using human skin M1 fibroblasts. The potential of the nanoclusters as dual magneto-photothermal agents was investigated by applying an alternating magnetic field (18 kA/m and 165 kHz) and/or NIR laser (850 nm, 0.75 W/cm2). Nanoclusters showed a size of 350 nm consisting of nonspherical magnetic particles of 11 nm completely coated with polydopamine. In addition, they were superparamagnetic and did not significantly affect cell viability at concentrations below 200 µg/mL. Finally, the SAR values obtained for the nanoclusters demonstrated their suitability for magnetotherapy and phototherapy (71 and 41 W/g, respectively), with a synergistic effect when used together (176 W/g). Thus, this work has successfully developed polymeric-coated magnetic nanoclusters with the potential for dual magneto-photothermal cancer therapy.