Biomedical and environmental applications of magnetic nanoparticles

All iron oxide nanoparticles were prepared by using the co-precipitation process. In brief, iron oxide nanoparticles were synthesized from iron chloride solutions (with ^{Fe 3+}/^{Fe 2+} ratio of 2 : 1) with the presence of ^NH ₄ ^OH or NaOH. Most of the manganite nanoparticles of ^La _0.7 ^Sr _0.15 ^Ca _0.15 ^MnO ₃ were prepared by using the conventional solid-state reaction method followed by a milling process and a secondary annealing treatment using ^La ₂ ^O ₃, ^SrCO ₃, ^CaCO ₃ and ^MnO ₂ powders as starting materials (SC900), while nanoparticles of ^Mn _1−x ^Zn _x ^Fe ₂ ^O ₄ ferrite (x=0.0–0.5) were synthesized by using the co-precipitation method with ^MnCl ₂, ^FeCl ₃ and ^ZnCl ₂ as the starting materials and NaOH as the precipitating agent (^Z ₁₀).

CS coated ^Fe ₃ ^O ₄ fluid (CSF) was prepared by chemical co-precipitation of ^{Fe 2+} and ^{Fe 3+} ions by NaOH in the presence of CS, according to the detailed procedure described in [9]. OL coated ^Fe ₃ ^O ₄ fluid (OLF) was prepared by multistep synthesis [10]. Briefly, OLF and CSF were synthesized by co-precipitation from iron chloride solution with an ^{Fe 3+}/^{Fe 2+} ratio of 2 : 1. Then, Curcumin (Cur, preliminarily solubilized in ethanol) was attached by adsorption on the ^Fe ₃ ^O ₄ surface of OLF/CSF. Thus, several types of ferrofluids without/with Cur were prepared for further fluorescent and magnetic imaging.

Ultraviolet-Visible (UV-Vis) spectra were recorded by a UV-Vis Agilent 8453 spectrophotometer in the range of 250–800 nm. Laser Scanning Confocal Microscope (LSCM) images with excitation light of 488 nm were collected using a ZEISS 510 LSCM with a 40× or 63× oil immersion objective. Magnetic properties were characterized by using a home-made Vibrating Sample Magnetometer (VSM) and a Physical Property Measurement System (PPMS, Quantum Design) at fields ranging from −20 to 20 kOe at 25 °^C, with an accuracy of 10^{−5  emu}. The images of a mice tumor were carried out by a Philips Intera 1.5 Tesla MR scanner (Netherlands) with a slice thickness of 3 mm on transversal and coronal planes, and using two sequences—T2-weighted and T1-weighted.

A commercial generator (RDO HFI 5 kW) was used to create an alternating magnetic field of amplitude from 40 Oe to 100 Oe at 219 kHz (figure 1). The induction coil has seven turns with 3 cm diameter and 11.5 cm length. Powder samples of weighed mass were dispersed in 0.5 ml of water and kept in a round-bottomed glass holder. A vacuum layer was used to insulate thermal exchange from the samples to the ambient medium. Temperature increases in the range from 0 °^C to 100 °^C and from 0 °^C to 200 °^C were measured by using an alcoholic thermometer and a Copper–Constantan thermocouple, respectively. The magnetic heating effect was thoroughly studied for several naked particles samples of all oxide materials and for the starch-coated magnetite nanosystem. The measured time period was from 20 to 30 min. The saturation temperature, T ^_s , was defined as the one gained at a heating time of 25 min.

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2.5.1. Adsorption of As on magnetite nanoparticles

2.5.2. Adsorption of Pb(II) on chitosan/magnetite composite

Table 1 presents characteristic parameters: magnetization at 1 Tesla (M_1^T ), coercivity (H ^_c ), Curie temperature (T ^_C ), particle diameter (D), specific loss power (SLP), and saturation temperature (T ^_s ) of the three samples of mangetite (^M ₆), manganite (^SC ₉₀₀) and spinel ferrite (^Z ₁₀) nanoparticles.

Figure 1 shows magnetization curves of magnetite NPs (figure 1(a)) and the two ferrofluids of polymer/magnetic NPs (figure 1(b)). All of the curves' behaviors indicate that the magnetic nanoparticles are of superparamagnetic type. The saturation magnetizations of the ^Fe ₃ ^O ₄/^ST and ^Fe ₃ ^O ₄/^CS are, respectively, of about 0.9 and 1.1 ^{emu  g −1}, which give calculated concentrations of magnetite NPs equal to 15 and 20 ^{mg  ml −1}, correspondingly.

Figure 2 shows MH curves measured for the starch-coated ^Fe ₃ ^O ₄ magnetic sample with various ^Fe ₃ ^O ₄/^ST concentrations.

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The dependence of the residual arsenic concentration in treated water on the size D of magnetite NPs is presented in figure 3. With particle diameter D decreasing from 20 to 7 nm, the residual arsenic concentration first decreases very strongly to get a minimum value (1.6 μ^{g  l −1}) at D∼12 ^nm, and then increases with a further decrease of D.

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The decrease in the residual As in the range of D=20–12 nm can be explained by the increase in particle adsorption due to the increase in surface area. With further decreasing D, although the adsorption of As continuously increases, the magnetic force starts to fail to overcome the Brownian motion and viscous drag in the MNPs–As ferrofluid.

Figure 4 shows a plot of C ^_e /q versus C ^_e for the case of adsorption of Pb(II) ions for ^pH=4, 5 and 6, from which the linearity fit gave the q ^_m values, respectively, of 49.55, 54.80 and 6.33 ^{mg  g −1} (q ^_m is the maximum adsorption of metal ions). These results permitted us to conclude that magnetite/chitosan nanocomposite beads could serve as a promising adsorbent for heavy metals.

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It is well known that surface coatings provide a steric barrier to prevent nanoparticle agglomeration and avoid opsonization (the uptake by the reticuloendothelial system (RES), thus shortening circulation time in the blood and MNPs' ability to target the drug to specific sites and reduce side effects). In addition, these coatings provide a means to tailor the surface properties of MNPs, such as surface charge and chemical functionality. Some critical aspects with regard to polymeric coatings that may affect the performance of an MNP system include the nature of the chemical structure of the polymer (e.g. hydrophilicity/hydrophobicity, biodegradation), its molecular weight and conformation, the manner in which the polymer is anchored or attached (e.g. electrostatic, covalent bonding) and the degree of particle surface coverage. A variety of natural polymers/surfactants have been evaluated for this purpose. The most widely utilized and successful coatings, in terms of in vivo applications, are dextran, PEG, chitosan (CS) and oleic acid (OL).

By conjugating ^Fe ₃ ^O ₄ with Cur, it can be logically expected that the conjugate can be used as a cancer drug and the drug uptake can be observed in situ by fluorescence as well as magnetic measurements. On the UV-Vis spectra (not shown), the Cur containing fluids exhibited an absorption band at a wavelength of around 425 nm. This UV absorption effect explains the green fluorescence observed under fluorescence microscope, as demonstrated in an example image measured for the OLF-Cur sample excited by 488 nm Argon laser.

Figure 5 presents the M(H) curves taken for CSF and CSF-Cur. On the basis of the saturation magnetization value of the non-coated ^Fe ₃ ^O ₄ NPs (M ^_s =70 ^{emu  g −1}), the ^Fe ₃ ^O ₄ concentration can be estimated as 17.5 and 14.7 ^{mg  ml −1} for CSF and CSF-Cur, respectively. It is worth noting that CSF and OLF are magnetically stable in distilled water for several weeks. However, in a physiological solution (e.g. 1×^PBS, ^pH=7.4), the stability of CSF and CSF-Cur deteriorated drastically to a few hours, whereas the OLF and OLF-Cur still maintained their remarkable stability, at least for 5–7 days.

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Further, to get a closer insight into the kinetics, ^Fe ₃ ^O ₄-Cur uptake was visualized by LCSM in situ images, taken at 1, 2, 4 and 6 h of incubation. As expected, the number of ^Fe ₃ ^O ₄-Cur taken up into macrophage cytoplasm increases clearly with incubation time. The green fluorescent color is noticeably seen surrounding the nucleus surface at 0.5–1 h, then appears increasingly inside the nucleus at 2–4 h and finally reaches its maximal intensity there at 6 h. Since the fluorescence intensity of Cur directly correlates to the internalization ability of ^Fe ₃ ^O ₄-Cur into cells, it can be concluded that the ^Fe ₃ ^O ₄-Cur particles are efficiently internalized (figure 6).

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To investigate whether these nanocarriers of CSF and OLF could be used advantageously for magnetic resonance imaging, tumor-bearing mouse were prepared by intra-peritoneal injection of thiopental. When tumors reached a size of about 8×11 ^mm, the nanoparticles (OLF-Cur) were introduced to the tumors by intra-tumor injection directly. A healthy mouse and a tumor-bearing mouse injected with the equivalent volume of PBS were used as controls. The mice were then imaged by the Philips Intera 1.5 Tesla MR scanner with a slice thickness of 3 mm on transversal using T2-weighted sequences. Each scanning took about 5–7 min. While there was almost no significant difference in the tumor's signal intensity as compared with the control, the intra-tumor injection of OLF-Cur resulted in reducing the MR signal intensity, which in turn made the invaded region black. Thanks to this contrast change, the tumor could easily be differentiated from the surrounding tissues.