Functionalized Ferrites for Therapeutics and Environmental Pollution Management

Abstract

Surface-functionalized ferrite materials are the ultimate products obtained from micro/nanofabrication of one or more metal containing magnetic iron-based oxides and their surface fine-tuning with suitable molecules for desired applications. Appropriate functionalization of ferrite surface often implants a wide range of application-specific physicochemical characteristics. Herein, we have discussed surface functionalization of ferrites with different organic molecules, inorganic oxides, metals, and polymeric materials. Impacts of surface functionalization on the dispersibility, biocompatibility, conductivity, photocatalytic activity, and pH responsiveness of ferrite particles and their therapeutic and environmental potentials are also highlighted. Then, some widely used and important functionalization routes like coupling, ligand exchange, polymer encapsulation, and sol-gel techniques are illustrated. Finally, a brief overview of biomedical and environmental pollutant mitigation efficacies of the functionalized ferrite compounds is emphasized.

1. Introduction

Ferrites are ferrimagnetic iron oxide-based materials consisting of a small portion of one or more other metallic elements such as Ba, Sr., Mn, Bi, Co, Ni, and Zn. Low-cost, easy formulation, and magnetism of ferrites make them a potential candidate for technological and biomedical applications. However, poor colloidal stability, high band gap energy, and absence of suitable surface functionality highly limit their practical applications. To address these issues, various strategies have been applied. Among them, surface functionalization of ferrites is one of the important methods, which offers better dispersion stability, magnetism, high processability, desired functionality for anchoring on demand molecules, and relatively lower band gap energy to ease photocatalytic reactions. Functionalized ferrites are widely studied materials in the fields of energy, electronics, magnetics, catalysis, and biomedical technology for the last several decades. Here, the functionalization strategies of ferrites and application potentials of functionalized ferrites in therapeutic delivery and catalytic degradation of different environmental pollutants will be illustrated based on the recent literature.

Recently, many technological advancements have been made by using ferrite materials in the fields of biomedical sciences and environmental pollutant remediation engineering. Ferrites are a distinct class of magnetic nanoparticles (MNPs) having the general formula of MFe₂O₄, where the tetrahedral cationic site is occupied by a divalent cation, M²⁺, and the trivalent Fe³⁺ ions occupy the octahedral cationic sites of the crystal lattice [1]. Ferrite NPs possess high surface energy-to-volume ratio and excellent superparamagnetic characteristics. Ferrites materials can be synthesized using various methods namely coprecipitation [2], thermal decomposition [3], microemulsion [4], hydrothermal [5], and sol-gel process [6]. Ferrites are often used as strong magnetic adsorbents, sensors, payload carriers, and imaging contrast agents. However, these practical applications inevitably hindered due to the colloidal instability of ferrites in the dispersing medium [7]. In such cases, appropriate surface modification of ferrite materials can prevent excessive aggregation and immature leaching from the reacting environment while enhancing or retaining their core magnetic responsiveness [1]. In this chapter, our focus is to summarize some ferrite-functionalizing materials and their synthesis routes keeping mainly their therapeutic and environmental pollution management applications in mind.

Some of the ferrite particles are inevitable in the field of therapeutic applications like nanocarrier for payloads, biosensor for disease diagnosis, hyperthermia [8], and environmental hazard materials management via separation by adsorption and photodegradation of pollutants [9]. Unique saturation magnetization, permeability, and structural anisotropic properties of MNPs make them quite desirable materials to the researchers for their widespread usages in biomedical and technological fields [10]. However, these properties are quite insufficient for effective usage, especially in the biomedical and environmental areas. Basically, fine-tuning the surface properties of the ferrite nanoparticles namely colloidal stability, aqueous dispersibility, biocompatibility and nontoxicity are the key properties for their reactivity towards the surrounding environments. These properties are also crucial for determining their application potentials in different fields [11]. Functionalization is a vital technique for tailoring the surface properties of nanoparticles with different organic and inorganic nanoscale materials through the covalent and noncovalent bonds [12]. The aim of functionalization is to enhance the physicochemical and biological characteristics of the resulting ferrites.

2. Widely used materials for surface functionalization

Surface functionalization of the magnetic ferrite nanoparticles serves the advantages of site specificity, enhanced colloidal stability, and biocompatibility [8]. A wide range of applications of ferrites has been achieved via the controlled tuning of their surface properties. Nevertheless, the aftermath of the modification process is severely controlled by the physical, chemical, and electrical properties of the incoming ligands, dopants, and coating materials. Hence, it is important to have an insight into some of the readily used functionalizing materials and their influences on the properties of ferrite particles. Figure 1 illustrates the classification of different functionalizing materials for the surface modification of ferrite NPs.

Figure 1.

Different materials used for ferrite functionalization.

2.1 Molecular organic compounds

There are many small organic molecules that are commonly used as stabilizing and functionalizing agents like amines and thiols for modification of the surface of ferrites. One such example is ethanolamine, which can modify the ferrite NP surfaces in a simple one-step process [13, 14]. The surface amine groups lower the hydrodynamic diameter (HDD) of the functionalized CoFe₂O₄ MNPs and facilitate their usage in biomedical applications [13]. The hardly basic nature of -NH₂ groups of MgFe₂O₄-NH₂ adsorbent helps in the selective chemisorption of different heavy metal ions (Pb²⁺, Cu²⁺, and Zn²⁺) via a complexation reaction [14]. For thiol functionalization, a mixture of tetraethyl orthosilicate (TEOS) and (3-mercaptopropyl)-trimethoxysilan is much desired by many researchers [15, 16]. It includes the silica coating of the ferrite core to which the -SH group is attached. Like amine functionalization, the heavy metal adsorption process of thiol-functionalized ferrites is influenced by the Lewis acid-base interactions [15].

Folic acid (FA) is a poorly water-soluble biologically important molecule. Its overexpression in the vast majority of cancer cells gives the FA-modified nanoparticles a better chance for internalization into the body and enhances the efficacy of targeted delivery of drug molecules. FA functionalization facilitates the pH-responsive release of the cationic anticancer drug doxorubicin (DOX) from cobalt ferrite magnetic nanoparticles (CFMNPs). At basic pH, FA is converted into folate ions and immobilizes a higher amount of DOX molecules. The acidic environment of cancer cells stimulates the breaking of this electrostatic interaction and enables the burst release of the DOX molecules [8]. FA is widely used for rendering cancer cell targetability to different anticancer drug nanocarriers [8, 17, 18]. Citric acid has been readily used in the synthesis of biocompatible magnetic fluids (BMFs) for enhanced colloidal stability of the nanoparticles [19, 20]. Citrate-coated cobalt (cit-CF) and nickel ferrite (cit-NF) nanoparticles exhibit a dose-dependent radiation cytotoxicity against MCF-7 cancerous cells and are considered a suitable radiosensitizer for cancer treatment [21]. Oleic acid (OA) is a type of fatty acid that is used as a surfactant and forms a dense protective shell layer around the nanoparticle surface during its functionalization process. In addition to its ambiphilic nature, OA imposes a non-immunogenic and anti-inflammatory environment on the attached nanoparticle. Cell viability studies by Sandeep et al. showed that only a minimum dose rate (8 mg/ml) of the OA-coated zinc ferrite (OA-ZNF) is required for effective hyperthermia therapy [22]. For effective biological applications, Nam et al. transferred the OA/oleylamine (OLA)-stabilized CoFe₂O₄ particles from hydrophobic to hydrophilic phase through the poly(maleic anhydride-alt-1-octadecene) (PMAO) encapsulation [23]. Porphyrin, an organic heterocyclic compound, is a promising photoredox catalyst and photosensitizer. Functionalization by porphyrins aids the photocatalytic activities of ferrite NPs due to the ease of electron transfer through their highly π-conjugated systems [24]. Parnian et al. demonstrated that a porphyrin derivative, meso-tetraphenylporphine-4,4′,4″,4″′-tetracarboxylic acid (TCPP), can significantly enhance the photocatalytic activity of polythiophene-coated ZnFe₂O₄ (TCPP/ZnFe₂O₄@PTh) nanocomposite [25].

Monodispersed MnFe₂O₄ NPs were functionalized with biotin and single-stranded DNA (ssDNA) for effective detection of protein or complementary ssDNA-patterned substrate. Here, the low magnetocrystalline anisotropy and a high moment of the NPs helped the bio-functionalization and in situ magnetic detection at room temperature in both in vitro and in vivo biological environments [26]. Biochar (pyrogenic black carbon) is recognized as a cost-effective adsorbent for environmental remediation due to its unique surface porosity and functionality. Excessive phosphate can seriously endanger aquatic bodies. Superparamagnetic magnesium ferrite (MgFe₂O₄)/biochar magnetic composites (MFB-MCs) remove phosphate from an aqueous solution through an inner-sphere complexation mechanism [27].

2.2 Widely used polymers

Polyglycerols (PG), also known as polyglycidols, are remarkably attractive candidates for surface functionalization due to their voluminous hydroxyl groups and flexible polyether backbone. Rimesh et al. used L-α-phosphatidylethanolamine (PE) block as a hyperbranched polyglycidol lipopolymer to provide water solubility and biocompatibility to hydrophobic oleylamine (OA)-stabilized manganese ferrite (MnFe₂O₄@OA) nanoparticles [17]. Debarati et al. functionalized dopamine-bound cobalt-ferrite (CF-DA) nanoparticles with polyethylene glycol (PEG). PEG functionalization prevented the early dissolution of DA in physiological conditions and facilitated its controlled release into the cancer cells [28]. Polyvinylpyrrolidone (PVP) is another well-known nanoparticle stabilizer and dispersant. Most of the bare ferrites lose their biological uses and superparamagnetic nature due to the excessive aggregation in the solution. PVP coating resists the formation of aggregated clusters of cobalt ferrites (CoFe₂O₄) making monodispersed and long-circulating MNPs. The as-prepared PVP-CoFe₂O₄ showcased lower cytotoxicity during the MTT assay [29]. Sahira et al. showed that PVP-induced biocompatibility increased the cellular uptake ability of MnZnFe₂O₄ nanoparticles [30]. Jaberolansar et al. proved that the nonmagnetic PVP matrix effectively handles the heat generated from the Co_0.3Zn_0.7Fe₂O₄ ferrite powder and enhances its usability for hyperthermia application [31].

The admirable film-forming ability, high transmembrane permeability, mechanical strength, nontoxicity, and biocompatibility of chitosan (CH) make it a useful nanoparticle stabilizing and functionalizing agent to attain a wide variety of applications. CH-coated CoFe₂O₄ nanocomposite can successfully immobilize horseradish peroxidase (HRP) for the effective detection of hydrogen peroxide (H₂O₂). Comparative studies with several existing studies proved that CH/CoFe₂O₄electrodes exhibit larger liner range (3 × 10⁻² to 8 mM), shorter response time (4 s), and enhanced sensitivity (23 nA/mM) [32]. Chitosan-functionalized CaFe₂O₄ MNPs possess 88.2% immobilization efficiency for ampicillin, which is mainly attributed to the electrophilic interactions of the protonated amino groups of CH moiety with ampicillin [33]. Moreover, Datna et al. reported that CH-coated CoFe₂O₄ MNPs exhibit stronger antimicrobial activity for both the Gram-negative P. aeruginosa and Gram-positive E. faecalis and E. coli than the uncoated ones [34]. Conducting polymers; such as polyaniline (PANI) and polypyrrole (PPy) comprise a useful group of materials for ferrite functionalization due to their tunable electrical properties and high physical flexibility. Experiments showed that the diamagnetic PANI coating enhances the electromagnetic shielding ability of MnZn ferrite (MZF) and NiMnZn ferrite (NiMZF) [35]. Sadeghinia et al. showed that the PANI filaments in the PANI/perlite-barium ferrite nanoparticles (PANI/PBF-NPs) cause a decrease in their surface areas and an increase in the pore volume. Thus, PANI contributes to the improvement of the electrical charge storage capability of the composite [36]. The extended p-conjugation of PANI with single- and double-bond alteration is responsible for its semiconducting nature that can facilitate the electrochemical properties of different spinel ferrites [37, 38]. Yan et al. showed that due to the dielectric loss of PANI/PPY coating, the saturation magnetization of the PANI(PPY)-BaFe₁₂O₁₉/Ni_0.8Zn_0.2Fe₂O₄ ferrite decreases while increasing its electrical conductivity [39].

2.3 Metallic doping

Substituting paramagnetic Co²⁺ ions with diamagnetic Zn²⁺ in the CoFe₂O₄ lattice profoundly impacts the magnetic aspects of the Co_1 − xZn_xFe₂O₄ compound. The as-synthesized mixed ferrite exhibits increased saturation magnetization and reduced anisotropy constant due to the dilution of spin moments by the Zn²⁺ ions [40]. Zn doping essentially improves the photocatalytic efficiency of ferrite NPs by lowering the band gap and reducing the recombination of photogenerated electrons and holes [41, 42]. Gold nanoparticles (Au NPs) possess rich surface chemistry for facilitating the healthcare-related application sectors. Au coating of ferrite NPs hinders the oxidation of the magnetic core and acts as a convenient platform for further surface functionalization. Juan et al. fabricated glyco-ferrites for MRI contrast agent application using bimetallic superparamagnetic XFe₂O₄@Au (X = Fe, Mn, and Co) nanocrystals. During the synthesis process, the Au shell forms stable thiol-Au bonds with the neoglycoconjugates [43]. Au NPs render biocompatibility along with tunable plasmonic characteristics to the superparamagnetic MgFe₂O₄. Such optical properties allow the easy detection of tissue and blood in the near-infrared (NIR) region for potential hyperthermia and drug delivery application [44].

2.4 Inorganic compounds

Cadmium sulfide (CdS)-coated ferrite nanocomposites are known to exhibit good photocatalytic activity for wastewater treatment. CdS is an n-type semiconductor with a large direct band gap under visible light irradiation. Ferrite nanoparticles improve the catalytic activity, anti-photocorrosion, recovery, and reuse of CdS catalyst. Together, this semiconductor-based photocatalysis formulates a green technology for environmental protection by degrading several organic dyes (e.g., 4-chlorophenol (4-CP), methylene blue (MB), Rhodamine B (RhB), and methyl orange (MO)) [45, 46]. Functionalization by the inert silica layer can screen magnetic dipole interactions between magnetic nanoparticles and in that way facilitate their aqueous dispersibility and biocompatibility for biomedical and bioengineering applications. The presence of abundant silanol groups at the silica-coated ferrite NP surfaces enables the scope for easy processability for multifunctional nanocomposite synthesis [47]. Banalata et al. tailored the mesoporous silica-coated superparamagnetic manganese ferrite (MSN) with 3-aminopropyl triethoxysilane (APTES) for amine functionalization, which is schematically shown in Figure 2. Next, the H₂N-MSN particles were conjugated with FA for targeted delivery of the anticancer drug, doxorubicin (DOX). The residual amine groups on the FA-MSN were labeled with the fluorescent dye rhodamine-B-isothiocyanate (RITC) for their cell internalization and detection. Hence, this functionalized entity can serve for cancer diagnosis and treatment [47].

Figure 2.

Step-by-step synthesis of silica-coated manganese ferrite for DOX delivery (MSN). Copyright: Journal of colloid and Interface science [47].

Ferrite-decorated graphene oxide (GO) nanocomposites are well dispersed in aqueous/physiological media and biocompatible in nature due to the high density of oxygen-containing groups, such as carboxylic, hydroxyl, and epoxide groups on the surfaces and edges of GO. The unique mechanical, electrical, and surface characteristics of GO nanosheet promote many theranostic applications [48]. Yan et al. demonstrated that GO/MnFe₂O₄ nanohybrids showcase exceptionally high loading capacity for DOX mainly due to the strong π–π stacking and hydrophobic interaction between the hexagonal lattice of GO and the extended aromatic chain of DOX. Furthermore, the drug release mechanism is controlled by the pH and NIR irradiation [49].

2.5 Carbon nanotubes (CNTs)

Ferrite NPs decorated on CNTs possess excellent electrical, thermal, and mechanical properties. CoFe₂O₄ modified acid-functionalized multiwalled carbon nanotubes (MWCNT-COOH) are effective RhB adsorbent. Increasing MWCNT-COOH content from 29 to 75% increases the presence of active sites for electrostatic interactions and eventually increases the adsorption capacity from 5.165 to 42.68 mg g⁻¹ [50]. On the other hand, Huixia et al. demonstrated the biomedical applications of MWCNT/CoFe₂O₄ nanocomposite. The strong supramolecular π–π stacking interaction between DOX and the side walls of CNTs results in its high loading capacity (about 75.2%). Moreover, a high T₂ relaxivity, low cytotoxicity, and pH-responsive drug release ability showcase the nanocomposite’s potential as synergistic cancer diagnostic and chemotherapeutic agent [51]. Yan et al. coated the magnetoelectric multiwall carbon nanotubes (MWCNTs)/Fe–Ni alloy/NF particles with 3,4-ethylenedioxythiophene and pyrrole (PPy-PEDOT) copolymers in a complex core–shell structure. The conducting network of MWCNTs and PPy-PEDOT nanofiller improves the impedance matching and interfacial polarization, making a promising microwave absorber for electromagnetic pollution remediation [52].

3. Common functionalization strategies for the surface functionalization of ferrite materials

3.1 Coupling method

Nanoparticle functionalization via coupling reaction always occurs in the presence of a common intermediate to facilitate the energy transfer from one end of the reaction to another. Chaitali et al. cingulated FA on the CFMNP surfaces after the activation of FA using 1-Ethyl-3-(3-dimethylaminopropyl)-carbodiimide (EDC) and N-hydroxysuccinimide (NHS) in a dimethyl sulfoxide (DMSO) dispersion [8]. FA molecules were conjugated with different natural cytotoxic drug-encapsulated bovine serum albumin-calcium ferrite nanoparticles (BSA-CFNP) by the EDC coupling method [18].

3.2 Ligand exchange reaction

It is a post-synthesis surface modification method where the ligands of a preformed material are exchanged with another compound. Rimesh et al. utilized this process to exchange OA molecules from the MnFe2O4@OA nanoparticles with FA-modified PE hyperbranched polyglycidol (PE-HBPG-FA) [17]. Similarly, Seung et al. employed the ligand exchange method for nonpolar to polar (water) solvent phase transfer of manganese ferrites (MnFe₂O₄) dispersed in hexane into single-layered poly(ethylene glycol)-coated MnFe₂O₄. After that, the nano dispersion was converted into double-layered oleylphosphate(OA)-functionalized MnFe₂O₄ nanocrystals via ligand encapsulation [53].

3.3 Polymer encapsulation

Another useful post-synthesis functionalization process is polymer encapsulation. In general terms, encapsulation refers to the process in which a bioactive material is enclosed in an inert matrix mainly for stabilization purposes [54]. Common polymers like PVP, PEG, and CH coating on ferrite molecules are fabricated by simple mixing of the reagents followed by the application of ultrasonication or continuous stirring [28, 30, 34]. Others occur via in situ polymerization method initiated by heat, radiation or other materials that can generate the radical reactions. Ammonium persulfate (APS) initiated aniline polymerization reaction in the presence of powdered CuFe₂O₄ in order to yield highly crystalline PANI/CuFe2O4 nanocomposite [37]. Polymethacrylate (PMAA) functionalization of nanocrystalline nickel ferrites (NiFe2O4) was carried out by potassium persulfate (K₂S₂O₈)-initiated polymerization reaction in an acidic reaction medium (pH ~ 3) [55]. Magnetoelectric core-shell nanocarrier for chemotherapeutic drug methotrexate was fabricated by functionalizing CoFe₂O₄–BaTiO₃, CoFe₂O₄–Bi4Ti₃O₁₂, and Fe₃O₄–BaTiO₃ with PNIPAm [56].

3.4 Solution casting method

This process is used in thin-film formation mainly for the uniform distribution of the functionalizing materials in the polymer matrix. It is a convenient laboratory-friendly process in which polymer film adhesion with the reinforcing material (i.e., ferrite NPs in this case) is achieved by dispersing the polymer and NPs in a common solvent medium. Next, the evaporation of the solvent leaves out the desired polymer-functionalized nanocomposite [57]. The inclusion of multicomponent CuFe₂O₄/Cu₂O/CuO NPs in the polymethyl methacrylate (PMMA) matrix was carried out for enhanced antibacterial properties. The NPs-PMMA dispersion in acetone solution cast on a slide resulted in an antibiofilm nanocomposite [58]. Jay et al. synthesized CH-functionalized nanostructured NiFe₂O₄ (n-NiFe₂O₄-CH) thin film onto the indium tin oxide (ITO) glass substrate via this simple method [59].

3.5 Sol: Gel coating

Also known as inorganic sol-gel coating that occurs via successive hydrolysis and polycondensation of the precursor material (sol) into a three-dimensional continuous network (gel). This method is preferable due to better control over nanoparticle size and stability and coating homogeneity [60]. Ashkan et al. synthesized zinc silicate-coated superparamagnetic zinc ferrite composite using the sol-gel method. In this work, a simple tuning of pH value into the basic medium of the reacting solution paved the way for Zn²⁺ and Si⁴⁺ ion adsorption onto the cetyltrimethylammonium bromide (CTAB)-modified surfaces of ZnFe₂O₄ nanoparticles. After that, the intermediate CTAB layer was eliminated with the help of ethanol solution yielding zinc silicate shell over the ZnFe₂O₄ core. Figure 3 shows the rough surface texture and microspherical size (100–300 nm) of the synthesized zinc silicate-ZnFe₂O₄ composite [61].

Figure 3.

The FESEM micrographs of ZnFe₂O₄ (a) and zinc silicate-ZnFe₂O₄ (b). Copyright: Ceramics international [61].

The sol-gel technique was utilized to yield a uniform coating of nanocrystalline TiO₂ shell around the CoFe₂O₄ MNPs core. Wuyou et al. induced the heterogeneous nucleation of TiO₂via a slow and gradual supersaturation of Ti(OC₃H₇)₄ ethanol in 1:10 water–ethanol suspension of CoFe₂O₄ [62].

3.6 Stöber method

The Stöber method is a facile process for uniform silica coating on a nanoparticle surface through a sol-gel strategy. In simple words, ammonia-mediated hydrolysis of tetraethoxysilane (TEOS) yields silanol monomers at the nanoparticle surface. After that, the neighboring silanol monomers are condensed into a siloxane network cluster [63]. Likewise, Kooti et al. utilized this method to coat CoFe₂O₄ with SiO₂. The inert silica layer was later used for anchoring a molybdenum Schiff base onto the complex surface in order to enhance the catalytic activity for the oxidation of alkene. Figure 4 shows the step-by-step reactions that occurred during the functionalization process [64].

Figure 4.

Schematic illustration of the Mo-salenSi@Si-CoFe₂O₄ MNP preparation. Copyright: Catalysis letters [64].

4. Therapeutic applications of functionalized ferrites

4.1 Targeted drug delivery (TDD)

TDD means the focused transportation of therapeutic agents into the diseased tissue without affecting other organs adversely. The enhanced permeability and retention (EPR) effect of the drug-conjugated nanocarrier system is a very crucial factor for TDD [65]. Ferrite NPs with their intrinsic responsiveness toward the external magnetic field smoothen the deposition, accumulation, and controlled release of immobilized drug to the targeted sites [66]. However, their surface modification accelerates this process by resisting aggregation, premature leakage of drug molecules, and removal of the MNPs by the organs via phagocytosis [65]. Figure 5 shows the both pH- and temperature-responsive DOX release profile of the FA-coated CFMNPs. Here, FA-conjugation helped to retain the nanoparticles’ stability even after the drug release experiment. Results showed that the relative drug release amount increased from ~38–60% by decreasing the solution pH from 7 to 5.5. Moreover, the heat generated by the applied AC magnetic field elevated the amount of released drug up to 95% [8].

Figure 5.

Time-dependent DOX release profile of FA-coated cobalt ferrite MNPs at (a) pH = 5.5 and (b) pH = 7 as a function of time under temperatures 37 and 44°C in phosphate buffer solution. Copyright: Chemphyschem [8].

FA modification significantly multiplies (~30 folds) the targeting effect of BSA-CFNP hybrids encapsulating bio-derived polyphenolic drugs hesperidin and eugenol. The magnetic CFNPs accounted for higher drug encapsulation efficiency (62.94% for hesperidin and 85.58% for eugenol). The BSA hybridization offered synergistic pH and magnetic responsiveness to the synthesized nanocarriers and helped the controlled and targeted release of drug molecules [18]. PEG-anchored CF-DA nanoparticles exhibited better cellular uptake into the cancerous cell line A549 than the unanchored ones. Results from the cell apoptosis, ROS generation, and actin cytoskeleton disruption study showed that CF-DA-PEG is able to produce more free radicals and cause mitochondrial dysfunction and actin cytoskeleton destruction inside the A549 cells [28].

4.2 Bioimaging

The magnetic spinel structure of ferrite NPs helps to shorten the spin-spin relaxation time (T₂-weighted) of surrounding water protons. This improves the contrast of the magnetic resonance (MR) image while real-time imaging of biological functions. The main problem here is the pharmacokinetic properties (biocompatibility, circulation time in the bloodstream, targetability, etc.) of the contrast agents [67]. Many researchers have tried to tailor the surface of the ferrite NPs with suitable functionalities to overcome this situation. PE-HBPG-FA hybrid-encapsulated MnFe₂O₄ MNPs are effective T2-weighted MRI contrast agents. This hyperbranched lipopolymer rendered water solubility and biocompatibility, whereas FA introduced tumor cell targetability to the synthesized spinel type MnFe₂O₄@PE-HBPG-FA MNPs. This composite exhibited a higher transverse relaxivity value (140.56 mM⁻¹ s⁻¹) than conventional superparamagnetic iron oxides [17]. Disodium tartrate dihydrate (T)-functionalized and variable Gd³⁺-doped MnFe₂O₄ (T-MnGd_xFe_2 − xO₄) is an active fluorophore and possesses magnetic field-dependent photoluminescence (PL) properties. The ligand-to-metal charge transfer (LMCT) between the small organic ligand T and the dopant Gd³⁺ causes the high saturation magnetization of TMnGd_0.10Fe_1.90O₄ and a maximum PL intensity at about 417 nm. Moreover, this magneto-fluorophore showcases minimum cytotoxic effects and first-order degradation kinetics against bilirubin (BR). BR is a yellowish pigment responsible for hyperbilirubinemia or jaundice [68].

4.3 Biosensor

Functionalized ferrites are used as biosensing materials either by their direct application onto the transducer materials or by dispersion in the targeted environment [69]. For example, CH-modified n-NiFe₂O₄ comprises an efficient cholesterol biosensor in human serum samples. Basically, the biocompatible CH matrix helps in the homogeneous dispersion of n-NiFe₂O₄ NPs over the ITO bioelectrode and thus provides an ideal platform for cholesterol esterase (ChEt) and cholesterol oxidase (ChOx) immobilization. Electrochemical response studies prove the faster electron communication, high selectivity, and repeatability features of ChEt−ChOx/n-NiFe₂O₄ − CH/ITO bioelectrode [59]. Functionalization by a mixture of amine and thiol groups serves as an intermediate layer between the superparamagnetic cobalt ferrite nanoparticle core and gold nanoparticles’ shell. The investigations by Marcos et al. show that the M₂(4NH₂-SH)Au particles are able to immobilize single-stranded peptide nucleic acid (ssPNA) oligomers for the detection of single nucleotide polymorphisms (SNPs) in DNA [70].

4.4 Hyperthermia for cancer treatment

Hyperthermia treatment (also called thermal ablation or thermotherapy) is a process for treating cancerous cells locally under elevated temperatures (41–45°C). Ferrite NPs are able to produce heat of this temperature range while kept under an external alternating current (AC) magnetic field due to hysteresis loss and eddy current [8]. PEG-modified cobalt ferrite/hydroxyapatite immobilizing 5-Fluorouracil (FU) drug is a multimodel nanocarrier for synergistic chemotherapeutic and hyperthermia treatment. The presence of an AC magnetic field causes the heating of the magnetic core of this nanoparticle, which in turn compels the PEG matrix to release the immobilized drug molecules into the targeted sites [71]. Prashant et al. fabricated OA-coated CoFe₂O₄ NPs for magnetic fluid hyperthermia treatment. OA functionalization complements the great saturation magnetization and high permeability characteristics of CoFe₂O₄ NPs with its biocompatibility and high colloidal dispersive nature. OA-CoFe₂O₄nanocomposites exhibit reduced hypothermia temperature and magnetization values than the unmodified compounds in the water-ethylene glycol fluidic media [10]. Izabell et al. synthesized azelaic acid (AZA)-encapsulated manganese ferrite and zinc ferrite (MnFe₂O₄-AZA and ZnFe₂O₄-AZA) MNPs for high-performance hypothermic measurement. This hydrophilic outer layer of the MNPs imposes a direct effect on their high saturation magnetization values at low temperatures [72].

4.5 Tissue engineering

Considering the effect of Zn and Si in healthy bone tissue development and osteoblastic gene expression, Ashkan et al. formulated a multifunctional core-shell zinc silicate-ZnFe₂O₄ composite for bone tissue regeneration after implantation. Cell compatibility study using osteoblast cell line (MG63) revealed the concentration-dependent cell viability of the compound. Zn²⁺ ions are responsible for the antimicrobial nature of the complex against both the Gram-positive and Gram-negative bacterial strains [61]. Glutaric acid-functionalized cobalt ferrite (CoFe₂O₄-GAPT) MNPs are efficient agents for the top-down characterization of phosphoproteins during advanced disease diagnosis. SDS-PAGE analysis of the MNPs incubated pig cardiac phosphoproteins, and comparing the results with other non-treated samples showcased that the GAPT ligands facilitate the specificity and quantification efficacy of the MNPs [73].

5. Environmental pollution management

5.1 Wastewater treatment

5.1.1 By heavy metal adsorption

Zhiqiang et al. decorated the rice bran-derived biochar with ethylenediamine-functionalized MgFeAlO₄ (RB@MgFeAlO₄-NH₂) MNPs for Ni²⁺ elimination from the wastewater. The amine functionalization enhanced the sorption affinity of RB@MgFeAlO₄-NH₂via complexation with the Ni²⁺ ions, whereas the biochar employed the ion exchange mechanism during the purification process. Ni²⁺sorption percentage is maximum at pH ~ 6 when Ni²⁺ ions can be electrostatically attached to the surface amino groups without the risk of precipitating from the solution [1]. Figure 6 depicts the fabrication of La³⁺-grafted and hexamethylendiamine-functionalized copper ferrite (CuFe₂O₄-2N-La) MNPs, which also showed high phosphate adsorption capacity (32.59 mg/g). A comparative study of the Langmuir adsorption isotherms of CuFe₂O₄ 2N and CuFe₂O₄-2N-La confirmed that La³⁺ ions have exerted a direct effect on increasing the phosphate decontamination rates from water bodies via the ligand coordination mechanism [7].

Figure 6.

Synthesis of CuFe₂O₄-2 N-La and comparison of phosphate adsorption efficiency of CuFe₂O₄2N and CuFe₂O₄-2 N-La using the Langmuir adsorption isotherms. Copyright: Science of the Total environment [7].

Figure 7 shows the reductive-adsorption and desorption behaviors of MnFe₂O₄ MNPs. Bilayered OP-optimized MnFe₂O₄ MNPs exhibit a highly specific sorption ability for uranium. Here, the unsaturated-unsaturated oleyl carbon chains form a compact layer around the MnFe₂O₄ particle surface, rendering superior colloidal stability of the MNPs in aqueous medium. This ordered organic coating of OP utilized both the chemisorption and reduction of U⁶⁺ into U⁴⁺ to maximize the sorption capacity of the MNPs [53].

Figure 7.

Illustration of uranium adsorption by the reduction of U⁶⁺ into insoluble U⁴⁺ (orange) on the surface of the nanocrystalline MnFe₂O₄. Copyright: Journal of Materials Chemistry A [53].

5.1.2 Photocatalytic activity

Tudisco et al. anchored the visible light-sensitive TCPP molecules onto the surfaces of ferroelectric bismuth ferrite (BFO) MNPs. The resulting organic–inorganic composite BFO@TCPP is an efficient agent for the photocatalysis of organic dyes found in industrial wastewaters. TCPP helps enhance the surface-modified MNPs’ catalytic activity by decreasing its band gap than free BFO and inhibiting raid recombination of the photogenerated electron–hole pairs. Moreover, the TCPP layer remained intact even after four degradation cyclic runs, indicating the stability and reusability of the BFO@TCPP particles [74]. TiO₂ is arguably one of the best semiconducting photocatalysts due to its chemical stability, nontoxicity, and enhanced photoreactivity. But it suffers from poor separation ability from the treated water. Wuyou et al. resolved this matter by functionalizing ferromagnetic CoFe₂O₄ nanoparticles with TiO₂ nanocrystals in a core–shell structure. The resulting nanocomposite’s photocatalytic activity can be increased by increasing the percentage of TiO₂ in TiO₂/CoFe₂O₄ [62]. GO-modified copper ferrite (GO/CuFe₂O₄) nanocomposite is another worthy candidate for water remediation. The electron and hole pairs in a two-dimensional GO sheet generated by photo illumination are responsible for the superior malachite green dye (MG) degradability of GO/CuFe₂O₄ (62.37%) from the polluted water. Here, the magnetic CuFe₂O₄ merely increased the recyclability of this photocatalyst (Figure 8) [75].

Figure 8.

Photocatalytic degradation mechanism of MG dye onto GO/CuFe₂O₄. Copyright: Materials today: Proceedings [75].

5.2 Gas sensing

Xingwei et al. coupled the n-type semiconductor copper ferrite (CuFe₂O₄) with PANI for the development of a high-performance NH₃ gas sensor. This binary nanoformulation exerted a synergistic p-n heterojunction effect by decreasing the depletion layer, thus improving the response value and recovery time for NH₃ detection (Figure 9). The NH₃-detecting alarm device constructed based on this nanocomposite can selectively identify NH₃ gas of concentration as low as 5 ppm [37]. Another p-n heterojunction conducting material was synthesized by the in situ polymerization of PANI on NF nanoparticles for liquefied petroleum gas (LPG) detection. PANI modification mitigates the high-power consumption problem of NF. PANI-NF nanocomposite can operate at room temperature and retain its stability for over a month [38].

Figure 9.

Schematic illustration of the p-n heterojunction between PANI and CuFe₂O₄. Copyright: Sensors and actuators: B. Chemical [37].

5.3 Supercapacitor (energy storage)

Barkha et al. synthesized glycol-functionalized reduced graphene oxide-cobalt ferrite (CoF-rGO)-based electrodes for superior energy storage application. CoFe₂O₄ possesses high structural anisotropy and specific capacitance (C_s) necessary for supercapacitor buildup but lacks in having low electrical conductivity. The glycol molecules improved the capacitance of CoF-rGO by increasing the surface wettability of the composite. Additionally, the incorporation of CoF into the graphitized structure facilitates the interlayer migration of ions by generating electric double layer during the intercalation-deintercalation process. As a result, rGO and CoF synergistically helped to retain 98% capacitance of the synthesized electrode material even after 2000 charge-discharge circles [76].

Similarly, NiFe₂O₄ MNPs suffer from low power performance despite being anode materials in pseudocapacitor devices. For this reason, Neha et al. utilized a covalent functionalization process using aryl diazonium salt to restore the interfacial stability of the MNPs. The modified NiFe₂O₄ MNPs showcase strong metal–ligand bonds that eventually assist their overall magnetic and electrochemical behavior. Electrochemical studies showed that the diazonium-functionalized pseudocapacitor electrode exhibits substantially higher specific capacitance (~1279 Fg⁻¹) than bare NiFe₂O₄ and (~82–90%) after 2000 cycles [77].

6. Conclusion and perspectives

For successful therapeutic and environmental application of surface-functionalized ferrite nanoparticles, a clear understanding of the interaction between the functionalizing materials and the MNPs is crucial. Functionalization of the MNP surface effectively enhances the homogeneous dispersion, pH and temperature responsiveness, cellular uptake ability, and biocompatibility of ferrites for biomedical applications. However, for environmental protection management, introducing a new component onto the ferrite NPs surface would increase their sorption affinity, catalytic activity, recyclability, and specific capacitance according to the properties of the incoming materials. Therefore, it is very reasonable to think that functionalized ferrites hold great potentials. However, researchers need to be focused on fabricating multifunctional composites for synergistic drug delivery, tissue regeneration, and real-time bioimaging. When it comes to the practical applications using different biosafe compounds for different purposes that will significantly decrease the administration frequency, immunotoxicity and genotoxiciti, and the overall cost of the treatment. Similarly, for environmental protection, the designed models should be one-pot products, batch-to-batch reproducible, and easily quality controllable. Otherwise, industrialists and related policymakers would not be encouraged to adopt the green technology offered by these functionalized ferrite compounds. Finally, with the fast-paced experimental growth, it is time to concentrate on the commercialization of these materials. Several in vivo preclinical as well as clinical adaptations for the systematic validation of MNPs are currently in motion, and hopefully, we will witness the results very soon.