The use of magnetic nanoparticles in hyperthermia, that is, heating induced by alternating magnetic fields, is gaining interest as a non-invasive, free of side effects technique that can be ...considered as a co-adjuvant of other cancer treatments. Having sufficient control on the field characteristics, within admissible limits, the focus is presently on the magnetic material. In the present contribution, no attempt has been made of using other composition than superparamagnetic iron oxide nanoparticles (SPION), or of applying surface functionalization, which opens a wider range of choices. We have used a hydrothermal synthesis route that allows preparing SPION nanoparticles in the 40 nm size range, with spherical, cuboidal or rod-like shapes, by minor changes in the synthesis steps. The three kinds of particles (an attempt to produce star-shaped colloids yielded hematite) were demonstrated to have the magnetite (or maghemite) crystallinity. Magnetization cycles showed virtually no hysteresis and demonstrated the superparamagnetic nature of the particles, cuboidal ones displaying saturation magnetization comparable to bulk magnetite, followed by rods and spheres. The three types were used as hyperthermia agents using magnetic fields of 20 kA/m amplitude and frequency in the range 136-205 kHz. All samples demonstrated to be able to raise the solution temperature from room values to 45 °C in a mere 60 s. Not all of them performed the same way, though. Cuboidal magnetic nanoparticles (MNPs) displayed the maximum heating power (SAR or specific absorption rate), ranging in fact among the highest reported with these geometries and raw magnetite composition.
Biomimetic magnetic nanoparticles mediated by magnetosome proteins (BMNPs) are potential innovative tools for cancer therapy since, besides being multifunctional platforms, they can be manipulated by ...an external gradient magnetic field (GMF) and/or an alternating magnetic field (AMF), mediating targeting and hyperthermia, respectively. We evaluated the cytocompatibility/cytotoxicity of BMNPs and Doxorubicin (DOXO)-BMNPs in the presence/absence of GMF in 4T1 and MCF-7 cells as well as their cellular uptake. We analyzed the biocompatibility and in vivo distribution of BMNPs as well as the effect of DOXO-BMNPs in BALB/c mice bearing 4T1 induced mammary carcinomas after applying GMF and AMF. Results: GMF enhanced the cell uptake of both BMNPs and DOXO-BMNPs and the cytotoxicity of DOXO-BMNPs. BMNPs were biocompatible when injected intravenously in BALB/c mice. The application of GMF on 4T1 tumors after each of the repeated (6×) iv administrations of DOXO-BMNPs enhanced tumor growth inhibition when compared to any other treatment, including that with soluble DOXO. Moreover, injection of DOXO-BMNPs in the tumor combined with application of an AMF resulted in a significant tumor weight reduction. These promising results show the suitability of BMNPs as magnetic nanocarriers for local targeted chemotherapy and as local agents for hyperthermia.
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.
In this paper, it is proposed that polymer-coated magnetic nanorods (MNRs) can be used with the advantage of a double objective: first, to serve as magnetic hyperthermia agents, and second, to be ...used as magnetic vehicles for the antitumor drug doxorubicin (DOX). Two different synthetic methodologies (hydrothermal and co-precipitation) were used to obtain MNRs of maghemite and magnetite. They were coated with poly(ethyleneimine) and poly(sodium 4-styrenesulfonate), and loaded with DOX, using the Layer-by-Layer technique. Evidence of the polymer coating and the drug loading was justified by ATR-FTIR and electrophoretic mobility measurements, and the composition of the coated nanorods was obtained by a thermogravimetric analysis. The nanorods were tested as magnetic hyperthermia agents, and it was found that they provided sufficiently large heating rates to be used as adjuvant therapy against solid tumors. DOX loading and release were determined by UV-visible spectroscopy, and it was found that up to 50% of the loaded drug was released in about 5 h, although the rate of release could be regulated by simultaneous application of hyperthermia, which acts as a sort of external release-trigger. Shape control offers another physical property of the particles as candidates to interact with tumor cells, and particles that are not too elongated can easily find their way through the cell membrane.
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.
The capacitive mixing procedure for energy extraction based on Double Layer Expansion (CDLE) belongs to the group of so-called CAPMIX techniques, which aim at obtaining energy from the salinity ...difference between fresh and sea waters. Specifically, the CDLE technique takes advantage of the voltage rise that occurs when sea water is exchanged for river water in a pair of porous electrodes which jointly behave as an electrical double layer supercapacitor. In this article, we deal with some experimental aspects that appear essential for optimizing the extracted energy, and have not yet been analyzed with sufficient detail. This investigation will help in evaluating those parameters which need to be fixed in a future CDLE device. These include the charging potential, the durations of the different cycle steps, the load resistance used, and the porosity and hydrophilicity of the carbon.
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•We focus on the optimization of CDLE for energy extraction from salinity differences.•Hydrophilic particles used in the electrodes provide the largest energy values.•Carbon particles with subnanometer pores are preferred to those with larger size.
The design of novel nanomaterials that can be used as multifunctional platforms allowing the combination of therapies is gaining increased interest. Moreover, if this nanomaterial is intended for a ...targeted drug delivery, the use of several guidance methods to increase guidance efficiency is also crucial. Magnetic nanoparticles (MNPs) allow this combination of therapies and guidance strategies. In fact, MNPs can be used simultaneously as drug nanocarriers and magnetic hyperthermia agents and, moreover, they can be guided toward the target by an external magnetic field and by their functionalization with a specific probe. However, it is difficult to find a system based on MNPs that exhibits optimal conditions as a drug nanocarrier and as a magnetic hyperthermia agent. In this work, a novel nanoformulation is proposed to be used as a multifunctional platform that also allows dual complementary guidance. This nanoformulation is based on mixtures of inorganic magnetic nanoparticles (M) that have been shown to be optimal hyperthermia agents, and biomimetic magnetic nanoparticles (BM), that have been shown to be highly efficient drug nanocarriers. The presence of the magnetosome protein MamC at the surface of BM confers novel surface properties that allow for the efficient and stable functionalization of these nanoparticles without the need of further coating, with the release of the relevant molecule being pH-dependent, improved by magnetic hyperthermia. The BM are functionalized with Doxorubicin (DOXO) as a model drug and with an antibody that allows for dual guidance based on a magnetic field and on an antibody. The present study represents a proof of concept to optimize the nanoformulation composition in order to provide the best performance in terms of the magnetic hyperthermia agent and drug nanocarrier.
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•Liposomes increase the colloidal stability of inorganic and biomimetic nanoparticles.•Magnetoliposomes reach the hyperthermia effective temperature in less than one minute.•Mixed ...magnetoliposomes improve the magnetic hyperthermia response.•Lipid cover disappears after hyperthermia treatment.•These mixed magnetoliposomes could be a potential agent for hyperthermia.
Recently, liposomes have been explored as a potential solution to improve the biocompatibility and the colloidal stability of magnetic nanoparticles. Protocols have been developed for producing magnetoliposomes of magnetite nanoparticles obtained inorganically (MNPs). However, the biomimetic synthesis of magnetite using heterologous proteins from magnetotactic bacteria has become a real alternative to produce novel biomimetic magnetic nanoparticles (BMNPs). Among these, the BMNPs obtained in presence of MamC protein from Magnetococcus marinus MC-1 have been proposed as excellent candidates to be potentially used as drug nanocarriers and as hyperthermia agents. However, their colloidal stability still needs to be improved while maintaining their magnetic properties intact. One possibility explored in this manuscript is to form magnetoliposomes that contain BMNPs. Indeed, the protocols developed for producing magnetoliposomes of MNPs need to be tested and modified to be able to include BMNPs. In this context, a protocol has been developed to produce both magnetoliposomes filled with MNPs and/or BMNPs and their potential as hyperthermia agents was tested. In fact, for the first time, these two types of nanoparticles were mixed in different proportions to test the composition that would optimize such as behaviour as hyperthermia agents. Interestingly, it was observed that the hyperthermia behaviour of the magnetoliposomes greatly improved if they were filled with a mixture of MNPs and BMNPs. These results indicate that these magnetoliposomes display optimal characteristics to become a potential agent for hyperthermia and that the opening of those liposomes could be externally controlled by applying an alternate magnetic field.
In this work we report on the synthesis and characterization of magnetic nanoparticles of two distinct origins, one inorganic (MNPs) and the other biomimetic (BMNPs), the latter based on a process of ...bacterial synthesis. Each of these two kinds of particles has its own advantages when used separately with biomedical purposes. Thus, BMNPs present an isoelectric point below neutrality (around pH 4.4), while MNPs show a zero-zeta potential at pH 7, and appear to be excellent agents for magnetic hyperthermia. This means that the biomimetic particles are better suited to be loaded with drug molecules positively charged at neutral pH (notably, doxorubicin, for instance) and releasing it at the acidic tumor environment. In turn, MNPs may provide their transport capabilities under a magnetic field. In this study it is proposed to use a mixture of both kinds of particles at two different concentrations, trying to get the best from each of them. We study which mixture performs better from different points of view, like stability and magnetic hyperthermia response, while keeping suitable drug transport capabilities. This composite system is proposed as a close to ideal drug vehicle with added enhanced hyperthermia response.
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