Abstract
Magnetite nanoparticles (MNPs) coated by branched poly (ethylene-imine) (PEI) were synthesized in a one-pot. Three molecular weights of PEI were tested, namely, 1.8 kDa (sample MNP-1), 10 kDa (sample MNP-2), and 25 kDa (sample MNP-3). The MNP-1 particles were further functionalized with folic acid (FA) (sample MNP-4). The four types of particles were found to behave magnetically as superparamagnetic, with MNP-1 showing the highest magnetization saturation. The particles were evaluated as possible hyperthermia agents by subjecting them to magnetic fields of 12 kA/m strength and frequencies ranging between 115 and 175 kHz. MNP-1 released the maximum heating power, reaching 330 W/g at the highest frequency, in the high side of reported values for spherical MNPs. In vitro cell viability assays of MNP-1 and MNP-4 against three cell lines expressing different levels of FA receptors (FR), namely, HEK (low expression), and HeLa (high expression), and HepG2 (high expression), demonstrated that they are not cytotoxic. When the cells were incubated in the presence of a 175 kHz magnetic field, a significant reduction in cell viability and clone formation was obtained for the high expressing FR cells incubated with MNP-4, suggesting that MNP-4 particles are good candidates for magnetic field hyperthermia and active targeting.
Highlights
Cancer remains one of the most challenging diseases, its treatment involving, when possible, a combination of surgical resection of the tumor with radiation therapy, chemotherapy, and/or immunotherapy
We have demonstrated that the one-pot solvothermal synthesis of magnetic nanoparticles (MNPs) from FeCl3·6H2O, sodium acetate, and ethane-1,2-diol in presence of polyamine polymer PEI is a reliable method to produce Magnetite nanoparticles (MNPs) with amino groups on the surface, preserving the magnetite crystal lattice and allowing the coupling of different functions without any previous derivatization
It is interesting to mention that the method proposed provides, in a single stage, magnetite nanoparticles coated with PEI in a stable manner, which is probably advantageous over methods based on the post-synthesis addition of PEI on already formed particles, often requiring repeated layer-by-layer stages
Summary
Cancer remains one of the most challenging diseases, its treatment involving, when possible, a combination of surgical resection of the tumor with radiation therapy, chemotherapy, and/or immunotherapy. This approach does not guarantee the complete eradication of the cancer, and it is not exempt from risk since normal tissues are damaged. The underlying biological processes induced by hyperthermia are not fully understood and the differential thermal sensitivity of tumor cells remains controversial [3,4,5,6], despite the efforts dedicated to study the mechanism of the cellular effects [7]. Severe hyperthermia treatments (43–45 ◦C) provoke oxidative stress, and irreversible injury occurs when the temperature reaches values above 48 ◦C for a period of time exceeding a few minutes [1]
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