Synergistic Photothermal-Chemotherapy Based on the Use of Biomimetic Magnetic Nanoparticles

Abstract

MamC-mediated biomimetic magnetic nanoparticles (BMNPs) have emerged as one of the most promising nanomaterials due to their magnetic features (superparamagnetic character and large magnetic moment per particle), their novel surface properties determined by MamC, their biocompatibility and their ability as magnetic hyperthermia agents. However, the current clinical application of magnetic hyperthermia is limited due to the fact that, in order to be able to reach an effective temperature at the target site, relatively high nanoparticle concentration, as well as high magnetic field strength and/or AC frequency are needed. In the present study, the potential of BMNPs to increase the temperature upon irradiation of a laser beam in the near infrared, at a wavelength at which tissues become partially transparent, is explored. Moreover, our results also demonstrate the synergy between photothermia and chemotherapy in terms of drug release and cytotoxicity, by using BMNPs functionalized with doxorubicin, and the effectiveness of this combination therapy against tumor cells in in vitro experiments. Therefore, the findings of the present study open the possibility of a novel, alternative approach to fight localized tumors.

Enhanced Cytotoxic Effect of TAT–PLGA-Embedded DOXO Carried by Biomimetic Magnetic Nanoparticles upon Combination with Magnetic Hyperthermia and Photothermia

“…The functionalization efficiency was 60% ± 10% for DOXO, in agreement with previous results [ 3 , 11 ]. These nanoassemblies were further characterized, showing sizes (measured by dynamic light scattering) of 160 ± 30 nm, an iep of ~6, and a high absorbance in the NIR region, also in agreement with our previous findings [ 16 ].…”

“…Previous studies have shown that both BMNPs and PLGA(BMNPs) are internalized via endocytosis when they are incubated with cells [ 16 , 22 , 34 ]. The cellular uptake was determined by estimating the Fe internalized into the cells after their incubation with the different nanoformulations (PLGA(BMNPs) and TAT–PLGA(BMNPs)).…”

“…Lastly, the solid precipitated was stored in HEPES buffer (HEPES 10 mM, NaCl 150 mM, pH 7.4) and sterilized. These BMNPs were previously characterized in [ 3 , 16 ], and they were shown to consist of pure stoichiometric magnetite with an average size of 39 ± 7 nm (sizes from 10 to 70 nm) and an isoelectric point (iep) of ~4.1. BMNPs exhibit a high absorbance in the near-infrared region (NIR), as determined by UV−Vis−NIR absorbance spectra, due to the electronic transitions between Fe 2+ and Fe 3+ .…”

“…The photothermal assay was performed as previously described in [ 16 ]. Briefly, HepG2 cells were seeded onto 12 well-plates at 300,000 cells per mL, and, identically to magnetic hyperthermia treatments, cells were incubated for 48 h at 37 °C with 30 μg/mL DOXO, TAT–PLGA(DOXO-BMNPs) (300 μg/mL BMNPs and 30 μg/mL DOXO), or culture medium as a control experiment.…”

“…Another mechanism also capable of inducing temperature elevation is called photothermal therapy, in which nanoparticles, when irradiated with a near-infrared (NIR) laser, absorb electromagnetic energy and convert it into heat. This makes it possible to produce hyperthermia with low laser powers and low concentrations of nanoparticles [ 13 , 14 , 15 , 16 ]. The individual application of magnetic and photothermal hyperthermia is currently being tested and studied.…”