Synthesis Protocol for Fe3O4 Nanoparticles

Research will be limited to:
- Product: Fe3O4 nanoparticles
- Reactants: FeCl2, FeCl3
- Method: Coprecipitation
- Stabilizers: Oleic acid, Citrate
- Parameters: Molar ratio, NaOH concentration, Temperature

Strategy: I will investigate the optimal synthesis parameters for Fe3O4 nanoparticles via coprecipitation, specifically focusing on the interplay between the Fe2+:Fe3+ molar ratio, NaOH concentration, and reaction temperature. Furthermore, I will look for protocols that detail the sequential or simultaneous addition of oleic acid and citrate to achieve dual stabilization or to compare their effects on particle size and colloidal stability.
Queries:
- Fe3O4 coprecipitation FeCl2 FeCl3 molar ratio NaOH concentration temperature
- oleic acid citrate stabilization Fe3O4 nanoparticles coprecipitation protocol
- effect of NaOH concentration on Fe3O4 nanoparticle size coprecipitation
- Fe3O4 synthesis 1:2 molar ratio FeCl2 FeCl3 temperature dependence
- surface modification Fe3O4 oleic acid vs sodium citrate coprecipitation

Executing 5 concurrent searches:
- Fe3O4 coprecipitation FeCl2 FeCl3 molar ratio NaOH concentration temperature
- oleic acid citrate stabilization Fe3O4 nanoparticles coprecipitation protocol
- effect of NaOH concentration on Fe3O4 nanoparticle size coprecipitation
- Fe3O4 synthesis 1:2 molar ratio FeCl2 FeCl3 temperature dependence
- surface modification Fe3O4 oleic acid vs sodium citrate coprecipitation

Found 8 papers. Key excerpts:

Synthesis of Fe3O4 nanoparticles and their magnetic properties — Yan Wei et al., 2012

1877-7058 © 2011 Published by Elsevier Ltd. Selection and/or peer-review under responsibility of Chinese Materials Research Society doi:10.1016/j.proeng.2011.12.498
Fe3O4 magnetic nanoparticles (MNPs) were synthesized by a co-precipitation method using sodium citrate and oleic acid as modifiers. Phase composition and microstructure analysis indicate that the sodium citrate and oleic acid have been successfully grafted onto the surface of Fe3O4 MNPs. The magnetic behaviors reveal that the modification can decrease the saturation magnetization of Fe3O4 MNPs due to the surface effect. Fe3O4 MNPs modified by sodiumcitrate and oleic acid show excellent dispersion capability, which should be ascribed to the great reduction of high surface energy and dipolar attraction of the nanoparticles. © 2011 Published by Elsevier Ltd. Selection and/or peer-review under responsibility of Chinese Materials Research Society Keywords: Fe3O4; magnetic nanoparticles; modification.
1. Introduction
Compared to atomic or bulky counterparts, nano-sized materials owe superior physical and chemical properties due to their mesoscopic effect, small object effect, quantum size effect and surface effect. Recently, Fe3O4 MNPs have been intensively investigated because of their superparamagnety, high coercivity and low Curie temperature[1–4]. In addition to these characterss, Fe3O4 MNPs are also non-toxic and biocompatible. Therefore, Fe3O4 MNPs have brought out some new kinds of biomedical applications
* Corresponding author. X.L .Deng Tel.: +86-10-62173403; fax: +86-10-62179977-2584. E-mail address: kqdengxuliang@bjmu.edu.cn. Co-Corresponding author:Yuanhua Lin Tel.: +86-10-62773741; fax: +86-10- 62771160. E-mail address: linyh@mail.tsinghua.edu.cn.
© 2011 Published by Elsevier Ltd. Selection and/or peer-review under responsibility of Chinese Materials Research Society Open access under CC BY-NC-ND license.
Open access under CC BY-NC-ND license.
633Yan Wei et

al. / Procedia Engineering 27 (2012) 632 – 6372 Y. Wei, et al. / Procedia Engineering 00 (2011) 000–000
such as dynamic sealing[5], biosensors[6], contrasting agent in magnetic resonance (MR) imaging[7], localizer in therapeutic hyperthermia[8] and magnetic targeted-drug delivery system[9], etc.
It is well known that it is very important to ensure the narrow size distribution, good dispersion and high magnetic response of Fe3O4 MNPs in tissue fluid for applications. However, magnetic attractive forces combined with inherently large surface energies (>100 dyn/cm) make them easy for the aggregation Fe3O4 MNPs in fluids. Therefore, lots of synthesized polymers[10-14] (e.g., poly (vinyl alcohol) phosphate, polyethylene glycol, polyamides, polyglycidyl methacrylate, poly(acrylic acid), chitosan (CS) and o-carboxymethylchitosan) were employed as coating agent in order to modify the surface of iron oxide particles. Although the polymeric coatings can reduce the aggregation of MNPs, they also increase the overall size of the particles and thus limit the expression of magnetic property, tissue distribution, metabolic clearance and penetration ability into interstitial spaces. So it is very important to develop an efficient surface-modification method for preparing Fe3O4 MNPs with narrow size distribution and excellent dispersion in aqueous or inaqueous solution using small moleculer compounds.
In this work, we developed an efficient modification method using sodiumcitrate and oleic acid for the synthesis of Fe3O4 MNPs with narrow size distribution and excellent dispersion in fluids. Fe3O4 MNPs were synthesized by a co-precipitation method at different temperatures, and modified with odiumcitrate and oleic acid respectively. The effect of temperature and modifiers on the crystal structure, morphology, dispersion and size distribution, and magnetic properties of Fe3O4 MNPs were investigated in detail.
2. Experimental
The reagents of analytic grade (FeCl3·6H2O, FeCl2·4H2O, NaOH and C2H6O) were used as raw materials. Chemical grade sodiumcitrate (Na3C6H5O7·2

H2O) and oleic acid (C17H33COOH) were used as modifiers. Four samples were prepared depending on their synthesis conditions (shown in Table 1). Firstly, FeCl3·6H2O and FeCl2·4H2O with molar proportion of 1:2 were dissolved in ethanol or deionized water maintained at different temperatures (Table 1), and then NaOH solution (3 mol·L-1) was added into the above solution using a peristaltic pump under constant magnetic stirring for 30 min, and the final pH was 10. Afterwards, the sodiumcitrate and oleic acid were respectively added into the suspensions to modify the obtained Fe3O4 MNPs for 12h. The substance obtained were aged and digested at maintained temperature for 30 min and cooled at room temperature. The resulted particles were magnetically separated and washed repeatedly with deionized water and ethanol until pH was 7. The products were then dried at 60 °C in vacuum for 6 h for further characterizations.
The crystal structure of as-prepared samples was analyzed by X-ray diffraction (XRD) with a Rigaku D/Max-C model diffractometer using Fe target. The molecular structure of Fe3O4 MNPs was characterized by a Perkin-Elmer Paragon 1000 Fourier transform spectrometer (FT-IR) at room
634 Yan Wei et al. / Procedia Engineering 27 (2012) 632 – 637 Y. Wei, et al. / Procedia Engineering 00 (2011) 000–000 3
temperature (25 °C).The magnetic property of Fe3O4 MNPs was measured using a vibrating sample magnetometer (VSM, LakeShore 7307). The morphology of the magnetite nanoparticles were determined using transmission electron microscopy (TEM, Hitachi H-600-II, Japan).
3. Results and discussion
XRD measurement was used to identify the crystalline structure of the products. As shown in Fig. 1, the XRD peaks can match well with the characteristic peaks of inverse cubic spinel structure (JCPDS 19- 0629), which indicate that the crystalline structure of Fe3O4 MNPs can be remained after the surface modification with sodium citrateand the oleic acid. The average crystallite size d calculated using the Debye–Scherrer equation d =

Size control of magnetite nanoparticles by organic solvent-free chemical coprecipitation at room temperature — Tomohiro Iwasaki et al., 2010

1. Introduction Magnetite (Fe3O4) is one of the most useful industrial materials because of its excellent magnetic properties, and Fe3O4 nanoparticles have been used in various industrial products, such as recording media, pigments, copying toners, etc. The efficiency of such industrial products greatly depends on the size of Fe3O4 nanoparticles. Thus, the particle size has been controlled to be suitable for their applications by means of various preparation techniques using chemical reactions under dry and wet conditions. In biomedical applications, particularly, precise control of the particle size is required. For example, for drug delivery system Lin et al. Citation1Lin, BL, Shen, XD and Cui, S. 2007. Application of nanosized Fe3O4 in anticancer drug carriers with target-orientation and sustained-release properties. Biomed. Mater., 2: 132–134.  [Crossref], [PubMed], [Web of Science ®], [Google Scholar] and Zhang and Misra Citation2Zhang, J and Misra, RDK. 2007. Magnetic drug-targeting carrier encapsulated with thermosensitive smart polymer: Core-shell nanoparticle carrier and drug release response. Acta Biomater., 3: 838–850.  [Crossref], [PubMed], [Web of Science ®], [Google Scholar] synthesised the Fe3O4 nanoparticles of about 20 nm and 5 nm using a liquid phase coprecipitation method and a thermal decomposition method, respectively. Wang et al. Citation3Wang, X, Zhang, R, Wu, C, Dai, Y, Song, M, Gutmann, S, Gao, F, Lv, G, Li, J, Li, X, Guan, Z, Fu, D and Chen, B. 2007. The application of Fe3O4 nanoparticles in cancer research: A new strategy to inhibit drug resistance. J. Biomed. Mater. Res. A, 80: 852–860.  [Crossref], [PubMed], [Web of Science ®], [Google Scholar] applied the Fe3O4 nanoparticles of about 20 nm synthesised by an electrochemical deposition method for cancer therapy. Many preparation methods of Fe3O4 nanoparticles developed so far have several significant problems. In many cases, the synthesis process is complicated and environment-unfriendly

organic solvents are often used, resulting in an increase in both production costs and environmental impact. However, coprecipitation techniques in water systems without using any organic solvents are promising as a useful preparation method because the synthesis process can be simplified and the environmental impact is relatively low. In widely used coprecipitation methods, hydroxides of ferrous and ferric ions, ferrous hydroxide (Fe(OH)2) and goethite (α-FeOOH), are coprecipitated as precursors in an alkaline solution at relatively low temperature. The molar ratio of ferrous ion to ferric ion is 0.5, corresponding to the chemical stoichiometric ratio of Fe3O4 formation reaction Citation4Lian, S, Wang, E, Kang, Z, Bai, Y, Gao, L, Jiang, M, Hu, C and Xu, L. 2004. Synthesis of magnetite nanorods and porous hematite nanorods. Solid State Commun., 129: 485–490.  [Crossref], [Web of Science ®], [Google Scholar]. Then the solid phase reaction between the hydroxides results in the formation of Fe3O4. Recent reports reveal that the size of Fe3O4 nanoparticles thus formed greatly depends on the concentration of ferrous and ferric ions Citation5Martínez-Mera, I, Espinosa-Pesqueira, ME, Pérez-Hernández, R and Arenas-Alatorre, J. 2007. Synthesis of magnetite (Fe3O4) nanoparticles without surfactants at room temperature. Mater. Lett., 61: 4447–4451.  [Crossref], [Web of Science ®], [Google Scholar] and the reaction temperature Citation6Wu, JH, Ko, SP, Liu, HL, Kim, S, Ju, JS and Kim, YK. 2007. Sub 5 nm magnetite nanoparticles: Synthesis, microstructure, and magnetic properties. Mater. Lett., 61: 3124–3129.  [Crossref], [Web of Science ®], [Google Scholar]. These results imply that the synthesis conditions influence greatly not only the Fe3O4 formation reaction but also the formation of Fe(OH)2 and α-FeOOH precip

itates. Accordingly, in order to control the size of Fe3O4 nanoparticles, the formation process of Fe(OH)2 and α-FeOOH precipitates should be also controlled. Kandori et al. Citation7Kandori, K, Fukuoka, M and Ishikawa, T. 1991. Effects of citrate ions on the formation of ferric oxide hydroxide particles. J. Mater. Sci., 26: 3313–3319.  [Google Scholar],Citation8Kandori, K, Uchida, S, Kataoka, S and Ishikawa, T. 1992. Effects of silicate and phosphate ions on the formation of ferric oxide hydroxide particles. J. Mater. Sci., 27: 719–728.  [Crossref], [Web of Science ®], [Google Scholar] reported that the formation and crystal growth of α-FeOOH colloids was influenced by the anionic species existing together with ferric ions in the solution. Therefore, the coexisting anions must play an important role in the formation of Fe3O4 nanoparticles, and the function of coexisting anions should be clarified for controlling the particle size. To our knowledge, however, there is no research focusing on the effect of coexisting anions in the synthesis of Fe3O4 nanoparticles using the coprecipitation method. Coprecipitation methods for preparing Fe3O4 nanoparticles also have a serious problem. The formed Fe3O4 nanoparticles tend to have relatively low crystallinity, leading to poor magnetic property, when the coprecipitation is carried out at low temperature. Thus, a heating process, such as annealing and hydrothermal treatment is often employed to improve the crystallinity Citation6Wu, JH, Ko, SP, Liu, HL, Kim, S, Ju, JS and Kim, YK. 2007. Sub 5 nm magnetite nanoparticles: Synthesis, microstructure, and magnetic properties. Mater. Lett., 61: 3124–3129.  [Crossref], [Web of Science ®], [Google Scholar],Citation9Wu, JH, Ko, SP, Liu, HL, Jung, MH, Lee, JH, Ju, JS and Kim, YK. 2008. Sub 5 nm Fe3O4 nanocrystals via coprec

Macromolecules with Different Charges, Lengths, and Coordination Groups for the Coprecipitation Synthesis of Magnetic Iron Oxide Nanoparticles as — Cheng Tao et al., 2019

1. IntroductionIn the past decade, the utilization of magnetic iron oxide (Fe3O4) nanoparticles as a T1-weighted contrast for magnetic resonance imaging (MRI) has received tremendous attention [1,2,3,4,5,6]. On the one hand, Fe3O4 nanoparticles have better biocompatibility compared to currently widely-used clinical Gd-chelate T1 contrast agents, such as Gd-DTPA and Gd-DTOA [7,8,9,10,11,12]. The Gd-chelates have great potential accumulative toxicity (e.g., nephrogenic systemic fibrosis) caused by the leaching out of the Gd ions from the chelate ligand [13], while the Fe3O4 nanoparticles can be degraded in the body and the released iron ions can be subsequently incorporated into iron pools and metabolic processes [10]. On the other hand, Fe3O4 nanoparticles with a small size and suitable surface state are able to display a high longitudinal relaxation rate (r1) [14,15,16,17,18], which can significantly improve the spatial resolution of the T1-weighted image for some special sites such as blood vessels and vascular organs. Nevertheless, small Fe3O4 nanoparticles without appropriate ligands decorated on the surface tend to form aggregation and subsequently display T2 rather than T1 contrast enhancement [19,20].To improve the T1 contrast performance and prevent the aggregation of nanoparticles in vivo, great efforts have recently been focused on the synthesis and surface modification of Fe3O4 nanoparticles [21,22,23,24,25]. The coprecipitation reaction of Fe2+ and Fe3+ ions under alkaline conditions is a traditional and widely-used method to fabricate Fe3O4 nanoparticles [26,27,28,29,30]. Compared with some other methods, such as thermal decomposition [31,32,33] and hydrothermal and solvothermal methods [34,35,36,37], coprecipitation is more convenient since it can be carried out in water phase without the further requirement of surfactant modification to improve the water-dispersibility of the obtained nanoparticles. Besides, similar to the approach of microwave-assisted synthesis [6,38], the coprecipitation method is a procedure that can be easily scaled up [

39]. However, because the reaction is carried out in water phase and the reaction speed is very fast for coprecipitation, controlling the size and preventing the aggregation of the produced Fe3O4 nanoparticles are always important and challenging issues [40]. Using functional macromolecule ligands as templates and stabilizers has proved to be an effective approach to overcome these challenges [37,39,40,41,42]. The affinity coordination groups, such as the hydroxyl and carboxylic acid groups from the macromolecule ligands, can coordinate with the iron ions and thus control the growth of the nanoparticle seed and prevent the aggregation of the produced nanoparticles [43]. For example, Rui et al. used poly(acrylic acid) to synthesize Fe3O4 nanoparticles with a small size and high relaxivity for in vivo T1-weighted imaging [39]. Li et al. developed poly(acrylic acid)-poly(methacrylic acid) for the synthesis of small Fe3O4 nanoparticles with good water-dispersibility and remarkable T1 contrast performance [26].To date, a great number of macromolecule ligands have been utilized as templates and stabilizers to fabricate hydrophilic small Fe3O4 nanoparticles as T1 contrast agents [26,27,44,45,46], but studies that concern the use of different charges and coordination groups of macromolecule ligands are still limited [47,48]. Indeed, the charges of macromolecule ligands are also an important parameter for controlling the size and preventing the aggregation of the Fe3O4 nanoparticles, since they usually correspond to the coordination affinity between the coordination groups and metal ions, and the electrostatic interaction between adjacent nanoparticles. In this work, we used three macromolecule ligands that possessed negative, positive and neutral charges with carboxylic acid, amino and hydroxyl groups, respectively, as templates and stabilizers for the coprecipitation synthesis of small magnetic Fe3O4 nanoparticles (Scheme 1), which showed differences in size, water-dispersibility, cytotoxicity and T1-weight contrast performance. 2. Materials and Methods 2.1. MaterialsFe(SO4)2·7H2O, FeCl3·6H2O and NH3 solution (25%) were obtained from Sigma Aldrich (Saint Louis,

MO, USA). Poly(allylamine hydrochloride) (PAH, average Mw ~ 17,500), poly(acrylic acid) (PAA, average Mw ~ 2000) and polyvinyl alcohol (PVA, average Mw ~ 20,000–30,000) were purchased from Alfa (Heysham, UK). All chemicals were used without further purification. 2.2. Synthesis of Fe3O4-PAH, Fe3O4-PAA and Fe3O4-PVA NanoparticlesThe synthetic procedures for Fe3O4-PAH, Fe3O4-PAA and Fe3O4-PVA nanoparticles were quite similar, excepting the use of different polymer ligands as templates and stabilizers. Typically, the polymer ligand (140 mg) was added to a 250 mL three-necked flask with 50 mL of deionized water, and then stirred for 1 h under N2 atmosphere to remove the oxygen in the flask. Then 0.25 mmol of Fe(SO4)2·7H2O (70 mg) and 0.52 mmol of FeCl3·6H2O (140 mg) were dissolved in 2 mL of deionized water, and injected into the three-necked flask. The above mixture was slowly heated to 90 °C, and then 5 mL of concentrated ammonia solution was rapidly injected under vigorous stirring. The reaction was kept at 90 °C for a further 2 h and then cooled down to room temperature. The black suspension was ultrafiltration centrifugation (with 10-k ultra-filtration centrifuge tube) and was washed with deionized water 3–4 times. 2.3. CharacterizationThe structure of the obtained Fe3O4 nanoparticles was determined by Powder X-ray diffractometer (PXRD, Bruker, D8 ADVANCE, Cu K-α, Brucker, Karlsruhe, Germany). To verify the macromolecule ligand coating, Fourier-transform IR spectra (Nicolet Avatar 370 FT-IR, Thermo Electron Corporation, Madison, WI, USA) with potassium bromide as pressed pellets was carried out on a Nicolet Avatar 370 FT-IR spectrophotometer. The hydrodynamic size and zeta potential studies were carried out on a Malvern Zetasizer Nano ZS (

Synthesis conditions and characterization of superparamagnetic iron oxide nanoparticles with oleic acid stabilizer. — Anggita Dipika Wulandari et al., 2022

Currently, magnetic nanoparticles have been used on diagnostic therapies, tumor hyperthermia, targeted drugs, radioactive therapies, improved tissue repair, cell labeling, and cell separation.[ 1 2 ] The magnetic nanoparticles have unique properties, mainly superparamagnetic iron oxide nanoparticles (SPIONs) due to superparamagnetic actions, chemical stability, magnetic properties, and good biocompatibility.[ 3 ] Magnetic properties of SPIONs can be found in the core size below 20 nm which is often called “superparamagnetism.”[ 4 ]
The particle size of SPIONs is obtained through a suitable synthesis method, one of which is the coprecipitation method which is widely chosen and considered in the synthesis of SPIONs because of its productivity and simplicity in the processing step. However, this method produces highly agglomerated SPIONs resulting in less effectiveness in biomedical application.[ 5 6 ] Therefore, controlling the particle size and particle distributions of SPIONs is very crucial to avoid the SPION agglomerations and becomes a determinant of the synthesis process. SPIONs with particle sizes more than 100 nm can lose their magnetic properties easily because of oxidation and high chemical activity.[ 7 ]
The addition of oleic acid (OA) as a stabilizer and surface effect in the synthesis of SPIONs is important in technological applications because it can control particle size and prevent aggregation between particles.[ 8 9 10 ] Furthermore, OA is not only used as a stabilizer but also to prevent oxidation so that it can protect the layer of SPIONs.[ 11 ] The previous research showed that optimization of stirring rate can affect the stabilization of SPIONs-OA.[ 12 ] However, there is no report about the dual optimization of OA concentrations and stirring rate. This study, therefore, ascertains whether the optimization of OA concentrations and stirring rate can produce stable SPIONs-OA.
FeCl 3 ·6H 2 O, FeCl 2 ·4H 2 O, OA, and ammonium hydroxide 25% were purchased from Merck, Singapore.
SPIONs were synthesized by using the coprecipitation method according to the previous literature with modification.[ 8 ] The process was carried out in the environment of the nitrogen atmosphere and used a molar ratio of Fe 3 +:Fe 2+ (2:1). The process started with dissolving FeCl 3 ·6H 2 O (

27.378 mM, 50 mL) and FeCl 2 ·4H 2 O (13.413 mM, 50 mL) in demineralized water and heated to 60°C. Then, the process used vigorous stirring at 750–12,000 rpm. After the temperature reached 60°C, the ammonium hydroxide 25% was added at a speed of 1 mL in 6 s until the color of the solution turns black and the pH value of the solution is 11. After 30 min, OA with different concentrations (0.75%, 1.5%, and 3% v / v ) was rapidly added to the reaction mixture and the temperature was raised to 80°C. After 1-h reaction, the suspension of SPIONs-OA was cooled and stored for further characterizations.
Hydrodynamic size, polydispersity index, and zeta potential of SPIONs and SPIONs-OA were measured by dynamic light scattering (DLS) using a Zetasizer Malvern Panalytical (Malvern Instruments, Malvern, UK) at room temperature.
The ultraviolet-visible (UV) spectroscopy spectra were recorded by JASCO V530. The spectra of SPIONs-OA and SPIONs were compared.
The morphology and structure of SPIONs-OA were observed by transmission electron microscopy using Hitachi HT-7700, Institut Teknologi Bandung. The SPIONs-OA was placed on a 20-nm Cu: carbon transmission electron microscope (TEM) mesh grid.
The chemical functional groups of SPIONs before and after OA coating were analyzed by Shimadzu Fourier transform infrared spectroscopy (FTIR) 840 OS. Samples were mixed with KBr before analyzing.
The crystallite size was calculated based on the X-ray diffraction (XRD) pattern by HighScore Plus software. The crystal structure of the SPIONs and SPIONs-OA was observed by XRD by using a PANalytical X’Pert.
The DLS measurement result of SPIONs-OA is presented in Table 1 and Figure 1 . The stirring rate and concentrations of OA affect the measurement result. The optimum result for hydrodynamic size, polydispersity index, and zeta potential is 83.71 ± 0.70, 0.215 ± 0.01, and −-50

.6 ± 0.61, respectively, with the addition of 1.5% v / v OA and synthesis using 750 rpm (SPIONs-OA design B). The physical appearance of SPIONs and SPIONs-OA design B was observed by the suspension color change. After 2-h incubation at room temperature, the SPION color changed from black to clear suspension. Meanwhile, the SPIONs-OA still formed the black suspension color, as shown in Table 2 .
Effect of oleic acid concentrations and stirring rate on dynamic light scattering results of superparamagnetic iron oxide nanoparticles with oleic acid stabilizer
SPIONs-OA: Superparamagnetic Iron Oxide Nanoparticles-Oleic Acid
Particle size of superparamagnetic iron oxide nanoparticles- oleic acid design B
Physical appearance of superparamagnetic iron oxide nanoparticles and superparamagnetic iron oxide nanoparticles with oleic acid stabilizer design B
SPION s -OA: Superparamagnetic Iron Oxide Nanoparticles-Oleic Acid, SPIONs: Superparamagnetic iron oxide nanoparticles
UV-visible spectroscopy analysis is shown in Figure 2 . The wavelenght of SPIONs showed spectral ranges between 330 and 450 nm, whereas OA represented maximum absorbance at 272.5 nm and 262 nm. Meanwhile, SPIONs-OA showed maximum absorbance at 273 nm and 373 nm.
Ultraviolet-visible spectrum of superparamagnetic iron oxide nanoparticles, oleic acid, and superparamagnetic iron oxide nanoparticles-oleic acid
The TEM analysis for SPIONs-OA is shown in Figure 3 . The SPIONs-OA formed clusters of different sizes. However, each particle size was observed under 20 nm.
Image of superparamagnetic iron oxide nanoparticles-oleic acid from a transmission electron microscope
The spectra of OA, SPIONs, and SPIONs-OA are shown in Figure 4 . For SPIONs-OA, the spectrum changed to lower frequencies at 3138 and 2935 cm ‒1 and showed Fe-O vibrations at 580 cm ‒1 whereas two bands of OA were shown at 2862 and 2928 cm ‒1 .
Fourier transform infrared spectroscopy spectra of superparamagnetic iron oxide nanoparticles, oleic acid, and superparamagnetic iron oxide

Modified chemical coprecipitation of magnetic magnetite nanoparticles using linear–dendritic copolymers — Zohre Zarnegar et al., 2017

IntroductionMagnetic nanoparticles (NPs), especially magnetite (Fe3O4), can be widely used in science, technology, and healthcare in applications such as cell separation (Citation1Zhu, X.; Zhang, L.; Fu, A.; Yuan, H. Efficient Purification of Lysozyme from Egg White by 2-Mercapto-5-benzimidazolesulfonic Acid Modified Fe3O4/Au Nanoparticles. Mater. Sci. Eng. C. 2016, 59, 213–217. doi: 10.1016/j.msec.2015.10.009 [Crossref], [PubMed], [Web of Science ®], [Google Scholar]), microwave absorption (Citation2Hekmatara, H.; Seifi, M.; Forooraghi, K. Microwave Absorption Property of Aligned MWCNT/Fe3O4. J. Magn. Magn. Mater. 2013, 346, 186–191. doi: 10.1016/j.jmmm.2013.06.032 [Crossref], [Web of Science ®], [Google Scholar]), magnetic resonance imaging (MRI) techniques (Citation3Hola, K.; Markova, Z.; Zoppellaro, G.; Tucek, J.; Zboril, R. Tailored Functionalization of Iron Oxide Nanoparticles for MRI, Drug Delivery, Magnetic Separation and Immobilization of Biosubstances. Biotechnol. Adv. 2015, 33, 1162–1176. doi: 10.1016/j.biotechadv.2015.02.003 [Crossref], [PubMed], [Web of Science ®], [Google Scholar]), recording materials (Citation3Hola, K.; Markova, Z.; Zoppellaro, G.; Tucek, J.; Zboril, R. Tailored Functionalization of Iron Oxide Nanoparticles for MRI, Drug Delivery, Magnetic Separation and Immobilization of Biosubstances. Biotechnol. Adv. 2015, 33, 1162–1176. doi: 10.1016/j.biotechadv.2015.02.003 [Crossref], [PubMed], [Web of Science ®], [Google Scholar]), ferrofluids (Citation4Lin, C

.L.; Lee, C.F.; Chiu, W.Y. Preparation and Properties of Poly(Acrylic Acid) Oligomer Stabilized Superparamagnetic Ferrofluid. J. Colloid Interface Sci. 2005, 291, 411–420. doi: 10.1016/j.jcis.2005.05.023 [Crossref], [PubMed], [Web of Science ®], [Google Scholar]), biological sensing (Citation5Li, N.; Hao, X.; Kang, B.H.; Xu, Z.; Shi, Y.; Li, N.B.; Luo, H.Q. Enzyme-free Fluorescent Biosensor for the Detection of DNA Based on Core-Shell Fe3O4 Polydopamine Nanoparticles and Hybridization Chain Reaction Amplification. Biosens. Bioelectron. 2016, 77, 525–529. doi: 10.1016/j.bios.2015.10.004 [Crossref], [PubMed], [Web of Science ®], [Google Scholar]), bioactive molecule separation (Citation3Hola, K.; Markova, Z.; Zoppellaro, G.; Tucek, J.; Zboril, R. Tailored Functionalization of Iron Oxide Nanoparticles for MRI, Drug Delivery, Magnetic Separation and Immobilization of Biosubstances. Biotechnol. Adv. 2015, 33, 1162–1176. doi: 10.1016/j.biotechadv.2015.02.003 [Crossref], [PubMed], [Web of Science ®], [Google Scholar]), catalysis (Citation6–8Safari, J.; Zarnegar, Z. Sulfamic Acid-functionalized Magnetic Fe3O4 Nanoparticles as Recyclable Catalyst for Synthesis of Imidazoles Under Microwave Irradiation. J. Chem. Sci. 2013, 125, 835–841. doi: 10.1007/s12039-013-0462-2 [Crossref], [Web of Science ®], [Google Scholar]Safari, J.; Zarnegar, Z.; Heydarian, M. Magnetic Fe3O4 Nanoparticles as Efficient and Reusable Catalyst for the Green Synthesis of 2-Amino-4H-

chromene in Aqueous Media. Bull. Chem. Soc. Jan. 2012, 85, 1332–1338. doi: 10.1246/bcsj.20120209 [Crossref], [Web of Science ®], [Google Scholar]Safari, J.; Zarnegar, Z. A Highly Efficient Magnetic Solid Acid Catalyst for Synthesis of 2,4,5-Trisubstituted Imidazoles Under Ultrasound Irradiation. Ultrasonic. Sonochem. 2013, 20, 740–746. doi: 10.1016/j.ultsonch.2012.10.004 [Crossref], [PubMed], [Web of Science ®], [Google Scholar]), and magnetic targeted therapy (Citation9Wang, C.; Huang, L.; Song, S.; Saif, B.; Zhou, Y.; Dong, C.; Shuang, S. Targeted Delivery and pH-Responsive Release of Stereoisomeric Anti-cancer Drugs Using β-Cyclodextrin Assemblied Fe3O4 Nanoparticles. Appl. Surf. Sci. 2015, 357, 2077–2086. doi: 10.1016/j.apsusc.2015.09.189 [Crossref], [Web of Science ®], [Google Scholar]). For future highly sensitive magnetic nanostructures and biological and pharmacological applications, Fe3O4 NPs with controlled size, shape, and a narrow size distribution are needed. Recently, research on the synthesis and application of Fe3O4 NPs in chemistry and pharmaceuticals has received particular attention (Citation10Feng, J.; Mao, J.; Wen, X.; Tu, M. Ultrasonic-Assisted in Situ Synthesis and Characterization of Superparamagnetic Fe3O4 Nanoparticles. J. Alloys Compd. 2011, 509, 9093–9097. doi: 10.1016/j.jallcom.2011.06.053 [Crossref], [Web of Science ®], [Google Scholar]). Several methods have been developed for the synthesis of magnetic Fe3O4 NPs, including chemical coprecipitation (Citation10–14Feng, J.; Mao, J.; Wen, X.; Tu, M. Ultrasonic-Assisted in Situ Synthesis and

An Overview of Synthesis and Structural Regulation of Magnetic Nanomaterials Prepared by Chemical Coprecipitation — Zelin Li et al., 2023

1. IntroductionIn recent years, magnetic nanomaterials have been widely used in production, including ultra-microsensors, catalysts, anti-cancer medicine, biological engineering, the electronics industry, and other fields. Therefore, the preparation and applications of magnetic nanomaterials are important research topics [1,2,3,4,5]. Magnetic nanomaterials have applications in various fields due to their large specific surface area, extremely small size, high magnetism, and other characteristics. For example, CoFe2O4 magnetic nanomaterials as sensors have wide functions, high sensitivity, and fast response, while nanoparticles have the advantages of miniaturization and high speed [6]. Fe3O4 nanopowder and nano nickel, cobalt, and nickel-cobalt alloy materials are widely used as catalysts in wastewater treatment, CO catalytic oxidation, etc. [7,8,9]. Fe3O4 particles with a size smaller than 10 nm can swim in blood vessels. Therefore, magnetic Fe3O4 nanoparticles are used to dredge cerebral thrombosis, clean up fat accumulation in cardiac arteries, and even kill cancer cells to fight cancer. Iron oxide nanoparticles are one of the most widely used magnetic nanomaterials in the biomedical field [3,10]. Nanomaterials are used in the electronics industry to make micro-computer components [11].There are many preparation methods for magnetic nanomaterials, such as coprecipitation, hydrothermal, sol-gel, atomization, carbonyl methods, and so on. However, the sol-gel method has some disadvantages, such as expensive raw materials, poor sintering between particles, high shrinkage during drying, and easy agglomeration. The low-temperature hydrothermal method is generally used to prepare oxide powder, and the medium of the hydrothermal method has some limitations, including high-temperature hydrothermal process equipment requirements, technical difficulties, and poor safety performance. The carbonyl method also has high environmental requirements and is used less [12,13,14]. Chemical coprecipitation has become one of the common methods for preparing magnetic nanomaterials. The chemical coprecipitation method can not only make fine and uniformly mixed raw materials but also has the advantages of low preparation cost and simple preparation. The product also has good performance. The general process is as follows:

select precipitant according to the substances to be precipitated → precipitate reactions → filtrate → wash → dry → obtain precipitates [15]. A flowchart of this process is shown in Figure 1. The chemical coprecipitation process is simple and suitable for large-scale industrial applications and the preparation of various nanomaterials. The main mechanisms of the preparation process are as follows [16,17].It is well known that the premise of new phase formation is the existence of metastable states, such as supersaturation, supercooling, or overheating states. Therefore, a large supersaturation can be achieved at the usual reaction concentration. Coprecipitation reaction is the precipitation of solids from the liquid phase. Figure 2a shows a diagram of the solution supersaturation with time. As seen in Figure 2a, precipitation can only be achieved with a certain supersaturation of the solution. Based on Figure 2b, one can draw the following conclusion: the higher the supersaturation, the easier the precipitates form [16,17,18].For certain supersaturation conditions, the solute molecules generated by the reaction will form new crystal nuclei during nucleation and growth. Conversely, the generated solute molecules will diffuse to the surface of the generated nuclei, and then arrange on the surface of the crystal nuclei according to the specific crystal structure to complete the crystal growth. Due to constant supersaturation, the crystal growth rate is the key to controlling molecular diffusion or molecular entry into the lattice on the crystal plane. The former is directly proportional to the supersaturation ratio, and the latter is related to the crystal interface structure. For the crystal particle growth process of oxide precursors obtained by the precipitation method, the crystal nuclei surface conforms to the rough and fine abrupt interface growth model due to low solubility and high supersaturation [17,18].In summary, it can be seen that the conditions for preparing nanomaterials by the chemical coprecipitation method are controllable and can usually be prepared in one step, which is very important for the application of the chemical coprecipitation method. Magnetic nanomaterials also play important roles in aerospace, military, magnetic materials, the battery industry, etc. To prepare magnetic nanomaterials using chemical coprecipitation, it is important to know which factors will affect the morphology, structure, size, and related properties of magnetic nanomaterials. These are the

key references for the preparation of magnetic nanomaterials [19,20].In this paper, the magnetic nanobiomaterials and magnetic nanocatalysts, magnetic nano wave-absorbing materials, nanoelectromagnetic materials, and magnetic nanoadsorbents prepared by the chemical coprecipitation method are summarized, and the effects of different conditions on the magnetic nanomaterials are discussed. This will promote the application of the chemical coprecipitation method and have profound significance for the in-depth understanding of magnetic nanomaterials. 2. Magnetic NanobiomaterialsMagnetic nanomaterials have good application prospects as biomaterials due to their small size, good biodegradability, biocompatibility, and stability. As biomaterials, magnetic nanomaterials are mainly used in the fields of magnetically targeted drugs, immobilized enzymes, cell separation, immunoassays, and gene therapy. Due to the exchange coupling and bias effects of magnetic nanobiomaterials, they have been widely used in magnetic resonance imaging, magnetic hyperthermia, and biosensors [21,22].Magnetic Fe3O4 nanomaterials have been used in clinical medicine. The magnetic Fe3O4 nanomaterials prepared by the chemical coprecipitation method have been studied by many researchers. The specific action process is described as follows. The raw material for preparing Fe3O4 nanopowder by chemical precipitation is soluble iron salt, which contains Fe2+ and Fe3+. Generally, ammonia water is used to adjust the pH value. At a certain temperature, a coprecipitation reaction occurs under intense magnetic stirring. After the reaction proceeds for a period of time, precipitation occurs, and then the products are filtered, washed, and dried, finally obtaining Fe3O4 nanopowder [5]. The general reaction is [2,6]

8OH− + Fe2+ + 2Fe3+ = Fe3O4↓ + 4H2O

(1)

There are many factors affecting the morphology, structure, and magnetic properties of magnetic nano Fe3O4. Chen et al. [23] studied the effects of reaction temperature, n(Fe2+)/n(Fe3+), and pH on the magnetic properties of Fe3O4 nanopowder. The pH has a great influence on magnetic properties. With the increase in pH, the

Synthesis of biocompatible iron oxide nanoparticles as a drug delivery vehicle — Krupa Kansara et al., 2022

IntroductionIron-based magnetic nanoparticles (NPs) such as magnetite (Fe3O4) have been studied in detail due to their unique properties, such as stability over time, biocompatibility, and sensitivity to magnetic field.1ChinSFIyerKSSaundersMEncapsulation and sustained release of curcumin using superparamagnetic silica reservoirsChemistry200915235661566519396886 [Crossref], [Web of Science ®], [Google Scholar]–3DandamudiSCampbellRBThe drug loading, cytotoxicity and tumor vascular targeting characteristics of magnetite in magnetic drug targetingBiomaterials200728314673468317688940 [Crossref], [Web of Science ®], [Google Scholar] They can potentially be used as magnetic targeted drug delivery carriers and magnetic resonance imaging contrast agents due to their high saturation magnetization, low toxicity, and biocompatibility.4PanBFGaoFGuHCDendrimer modified magnetite nanoparticles for protein immobilizationJ ColloidInterface Sci2005284116 [Crossref], [Web of Science ®], [Google Scholar] The magnetic properties of Fe3O4 NPs are attributed to their size and size distribution, which, in turn, is dependent on the route of synthesis.Therefore, in this study, an attempt was made to synthesize Fe3O4 NPs using a safe-by-design approach by the coprecipitation method. Polyethylene glycol (PEG) was used as surfactant to control the particle size and narrow size distribution. The biocompatibility of Fe3O4 NPs was evaluated by cytotoxicity assays and cell cycle analysis in the human breast adenocarcinoma cell line (MCF-7).
Materials and methodsMaterialsFerric chloride hexahydrate and ferrous sulfate were purchased from SD-Fine-Chem. Ltd, Mumbai, India. Ployetheleneglycol (PEG-6000), dimethylesulphoxide, sodium hydroxide (NaOH), minimum essential medium eagle, phosphate-buffered saline, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), and antibiotic-antimycotic solution were purchased from HiMedia Laboratories Pvt.

Ltd., (Mumbai, India). The MCF-7 cell line was purchased from the National Centre for Cell Sciences, Pune, India.Fe3O4 NP synthesisThe preparation of Fe3O4 NPs was performed by a chemical coprecipitation method of Fe2+ and Fe3+ ions (1:2 molar ratios) by the addition of NaOH.5HarianiPLFaizalMRidwanMarsiSetiabudidayaDSynthesis and properties of Fe3O4 nanoparticles by co-precipitation method to removal procion dyeInt J Environ Sci Develop201343336340 [Crossref], [Google Scholar] A total volume of 15 mL of 0.25 M Fe2+ and 0.5 M Fe3+ solutions were prepared in deionized water. PEG was then added and the temperature slowly risen up to 80°C. During the initial 2 minutes of the reaction, NaOH was added to achieve a pH of 10. The reaction was allowed to continue on a magnetic stirrer for 2 hours. Thereafter, the suspension was centrifuged and washed several times with deionized water to lower the pH to 7. Finally, the particles were suspended in 10 mL of dimethylesulphoxide.Characterization of Fe3O4 NPsOne milliliter of the stock suspension of Fe3O4 NPs was diluted in 10 mL complete minimum essential medium eagle. The hydrodynamic size and zeta potential were determined using Zetasizer Nano ZS.Cytotoxicity assessmentThe cytotoxic potential of Fe3O4 NPs was assessed in MCF-7 cells after 6 and 24 hours of treatment using MTT and neutral red uptake (NRU) assays as described by Mosmann6MosmannTRapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assayJ Immunol Methods1983651–255636606682 [Crossref], [Web of Science ®], [Google Scholar] and Borenfreund and Puerner, respectively.7BorenfreundEPuernerEToxicity determined in vitro by morphological alterations and neutral red absorptionToxicol Lett1985242–31191243983963 [Crossref], [Web of Science ®], [Google Scholar]Cellular internalization of NPsThe internalization of

Fe3O4 NPs in MCF-7 cells was assessed according to the method described in our earlier study.8KansaraKPatelPShahDTiO2 nanoparticles induce DNA double strand breaks and cell cycle arrest in human alveolar cellsEnviron Mol Mutagen201556220421725524809 [Crossref], [Web of Science ®], [Google Scholar]Cell cycle analysisThe effect of Fe3O4 NPs on cell cycle was assessed according to the method described in our earlier study.8KansaraKPatelPShahDTiO2 nanoparticles induce DNA double strand breaks and cell cycle arrest in human alveolar cellsEnviron Mol Mutagen201556220421725524809 [Crossref], [Web of Science ®], [Google Scholar]
Results and discussionThe mean hydrodynamic size and zeta potential of synthesized Fe3O4 NPs were 98.19±1.0 nm and 36±2 mV, respectively. Flow cytometric analysis revealed a significant (P<0.05) increase in the internalization of Fe3O4 NPs in MCF-7 cells after 24 hours exposure at the two higher concentrations, as evident by an increase in the side scatter intensity (Figure 1). Synthesis of biocompatible iron oxide nanoparticles as a drug delivery vehicleAll authorsKrupa Kansara, Pal Patel, Ritesh K Shukla, Alok Pandya, Rishi Shanker, Ashutosh Kumar & Alok Dhawanhttps://doi.org/10.2147/IJN.S124708Published online:10 October 2022Figure 1 Internalization of Fe3O4 NPs in MCF-7 cells using flow cytometry.Notes: Data are expressed as mean ± standard error of the mean from three independent experiments. P<0.05, when compared with control.Abbreviations: NPs, nanoparticles; MCF-7, human breast adenocarcinoma cell line.Display full sizeFigure 1 Internalization of Fe3O4 NPs in MCF-7 cells using flow cytometry.Notes: Data are expressed as mean ± standard error of the mean from three independent experiments. P<0.05, when compared with control.Abbreviations: NPs, nanoparticles; MCF-7,

Surface Modification of Magnetic Iron Oxide Nanoparticles — Nan Zhu et al., 2018

1. IntroductionRecently, magnetic nanoparticles is an emerging field of study and has gained much attention among researchers due to their widespread applications in various fields including catalysis [1], data storage [2], environmental remediation [3], magnetic fluids [4], electronic communication [5], and biomedicine [6] etc. Among different types of magnetic nanoparticles (MNPs), iron oxide nanoparticles (IONPs) are the most popular and widely used in the field of biomedicine due to their ease of surface modification, synthesis, and low toxicity [7]. Current studies and literature have confirmed that magnetic IONPs are frequently used in the treatment of hyperthermia [8,9,10] or as drug carriers in cancer treatment [11,12,13], magnetic resonance imaging (MRI) agents [14,15,16], bioseparation [17,18,19], gene delivery [20,21,22], biosensors [23,24,25], protein purification [26,27,28], immunoassays [29,30,31] and cell labeling [32,33,34].However, IONPs suffer from two major issues such as rapid agglomeration, oxidation into the physiological environment of the tumors due to large surface area, chemical reactivity and high surface energy, thus resulting in a loss of magnetism [35]. Therefore, appropriate surface modification of IONPs is required to make them biocompatible. The coating method is the most common surface modification approach to conjugate the organic or inorganic materials onto the surface of IONPs. This method not only prevents the oxidation and agglomeration of IONPs, but also provides the possibility for further functionalization [36]. Functionalization of magnetic IONPs can improve their physicochemical properties, making them ideal candidates for the field of catalysis and biomedicine.Different characteristics such as size, shape, morphology and dispersability of the IONPs can affect their application in biomedicine [37,38]. Therefore, researchers are focusing on synthesizing MNPs by adopting different routes to control their size, shape and morphology with adjustable and desirable properties. So far, a number of synthesis routes such as co-precipitation [39], hydrothermal [40], thermal decomposition [41], microemulsion [42], electrochemical deposition [43], laser pyrolysis [44],

solvothermal methods [45], sonochemical methods [46], chemical vapor deposition [47], the microwave assisted method [48], and aerosol pyrolysis [49] have been reported to prepare the magnetic IONPs. The advantages and disadvantages of some methods are listed in Table 1.In this review, first we briefly describe the factors influencing why surface modification of MNPs is essentially required, and then introduce the structures of magnetic iron oxide nanocomposites. The materials used in surface modification are categorized as organic materials and inorganic materials. Organic material molecules are composed of small molecules and polymers while inorganic materials include silica, carbon, metals and metal oxides/sulfides. In next section, we summarize the IONPs’ surface coating mechanisms as well as the progress made in recent years, and highlight their applications in various fields. 2. Surface Modification of Magnetic Iron Oxide Nanoparticles (IONPs) and ApplicationsThere are four main purposes of surface modification of NPs: (1) to improve or change the dispersion of MNPs; (2) to improve the surface activity of MNPs; (3) to enhance the physicochemical and mechanical properties; and (4) to improve the bicompatibility of MNPs. There are mainly four magnetic iron oxide nanocomposites (Figure 1) [50]. 2.1. Surface Coating with Inorganic Materials 2.1.1. SilicaSilica is the most common and widely used agent for surface modification of IONPs [51,52,53,54,55]. Silica coating has following advantages: low agglomeration, enhancing the stability and reducing the cytotoxic effects of MNPs. Therefore, it has demonstrated good biocompatibility, hydrophilicity and stability [56]. Recently, researchers have described the procedure to control the size and thickness of the silica coated NPs [57]. Generally, there are four main approaches to prepare IONP@SiO2 (Table 2) [50].The Stöber method is the most common approach to synthesize IONP@SiO2, in which the IONPs are uniformly dispersed in ethanol solution, followed by the addition of tetraethoxysilane (TEOS), then finally the aqueous ammonia solution is admixed to the mixed solution [50,58]. As a basic catalyst, ammonia can not only control the particle

size, but also inhibit hydrolysis to form particles with regular morphology. Zhao Li et al. found that the size of silica particles increases with the concentration of ammonia, water, and TEOS in the reaction solution. At the same time, she found that an increase in the reaction temperature accelerated the ripening of the silica particles, causing the particle size to increase slightly [59]. This method can be applied to coat a SiO2 layer directly onto the surface of Fe3O4. Malvindi et al. studied the toxicity of silica-coated IONPs in a vitro model. They used the A549 and HeLa lines and incubated cells with surface-modified Fe3O4@SiO2 as well as bare NPs. They reported that the naked NPs show higher toxicity due to their stronger in situ degradation [60]. Uribe Madrid et al. demonstrated the synthesis of Fe3O4@mSiO2 core-shell structures with high specific surface area and different mesoporous silica (mSiO2) shell thickness. This composite nanoparticle synthesized via the modified Stöber method shows excellent drug release performance and it is ideal for targeted drug delivery in vivo [61].The second method is the microemulsion method, which can be divided into two different types, namely water-in-oil (W/O, micelles) and oil-in-water (O/W, reversed micelles). Sillca-coated IONPs with high crystallinity can be synthesized by the microemulsion process, which comprises water, oil and surfactant [62]. Du et al. synthesized a silica-encapsulated Fe3O4 core-shell structure by the microemulsion approach and further functionalized with an antiseptic agent cetyl trimethylammonium bromide (CTAB). Their results have shown that the core size of Fe3O4 NPs depends on the water/surfactant molar ratio of the microemulsion system [63]. Yang et al. developed an oil–water two-phase layered coating strategy for the preparation of monodisperse dendritic mesoporous silica-encapsulated magnetic nanospheres with pore size of approximately 5.7 to 10.3 nm and shell thickness of 40 to 100 nm [64]. Some researchers have put forward their own views on the mechanism of