Catalysts are one of the fundamental pillars of the chemical industry and have been widely applied in chemical synthesis, energy storage and conversion, biomedical applications, and environmental remediation ^[1][2][3][1,2,3]. Nanomaterials, which have nano-size intriguing physicochemical properties compared with their bulk materials and excellent reactivities and selectivities, are becoming more and more extensively adopted as catalysts [4]. Conversely, Nanoparticles (NPs) tend to aggregate, which can result in a severe reduction in catalytic activity, and the removal of nanoscopic catalysts from reaction media can be challenging ^[5][6][5,6]. Therefore, NPs with a desirable catalytic activity are commonly loaded in/on a solid support-yielding supported nanocatalyst, and the NPs can be separated from the product accompanying the recovery of support if necessary ^[7][8][7,8]. Aside from NPs, catalysts can also come in the form of water-soluble inorganic matters or organic polymers, such as silicate, transition metal complexes, and ionic liquids (ILs) ^[9][10][11][9,10,11]. It is evident that green chemistry and environmental protection demand the recovery and reuse of catalysts. In addition to the cost-related factors and operation procedures, it has been suggested that catalysts are easily and completely separated from the product and recycled further ^[12][13][12,13]. In heterogeneous catalytic reaction systems, supported nanocatalysts can be separated via centrifugation and sedimentation with special separation equipment, which is time-consuming and results in poor recovery and decreased reuse ability of the catalysts [14]. In homogeneous catalytic reaction systems, well-dispersed catalysts are even more difficult to separate due to its homo-phase state with reaction system [15]. Therefore, the design of easily separable catalysts is an extremely challenging issue which has received tremendous attention, especially for nanocatalysts and ILs. In order to separate the nanocatalysts from the reaction media, targeting a controllable delivery of the NPs, a feasible solution involves developing magnetic recyclable catalysts, which can contribute to efficient separation and convenient recycling [16].

In recent years, magnetic NPs based on Fe, Co, Ni, and Mn have been evaluated as promising materials in the field of catalysis, detection, electrochemistry, cancer treatment, biophysics, and functional materials ^[17][18][17,18]. Iron, which is the second most abundant metallic element on the earth, is low-cost and eco-friendly, and materials based on iron have attracted much attention in these fields [19]. Among iron oxides, such as magnetite (Fe₃O₄), FeO, FeS₂, γ-Fe₂O₃, and FeTiO₃, Fe₃O₄ are more commonly used, not only because of their properties regarding a high degree of spin polarization at the Fermi level, high Curie temperature (850 K), and electrocatalytic activity, but also because they are stable and synthesize easily ^[20][21][22][20,21,22].

Aside from the above-mentioned properties inheriting bulk from Fe₃O₄, nano-sized Fe₃O₄ have many other characteristics, such as a high size-controllability, high shape-controllability, high specific surface area, high magnetothermal conversion, and enzyme-mimetic activity of peroxidases and catalase (Table 1). Synthesis methods for Fe₃O₄ NPs include hydrothermal, sol–gel procedure, coprecipitation, thermal decomposition, microemulsion, biosynthesis, and so on [23]. Fe₃O₄ NPs with the required size (2–100 nm) and desired geometry (spherical, cubic, rod, hollow, or 2D nanoplate) can be precisely controlled in thermal decomposition and microemulsion methods [24]. Additionally, the functionalities of Fe₃O₄ NPs, such as stability, biocompatibility, catalytic activity, and oxidation resistance, can be improved by modifying the surface with additives and dopants ^[25][26][25,26].

Moreover, as Fe₃O₄ NPs have no residual hysteresis, they can be magnetized and aggregate immediately in the presence of a magnetic field and reach disaggregation immediately in the absence of a magnetic field [32]. This on and off switch character deriving from their superparamagnetism behavior has promoted their use in recoverable and recyclable techniques, especially in catalysis [33].

Studies showed that ~10/100 nm-sized bared Fe₃O₄ NPs and coated Fe₃O₄ NPs (L-cysteine, 3-(triethoxysilyl) propylsuccinic anhydride, 3-aminopropyl triethoxysilane, graphitic carbon nitride) demonstrated relatively low toxicity, and did not affect the long-term survival and welfare of the animals at concentrations of 0.001–1 mg/mL ^[34][35][157,158]. Fe₃O₄ NPs at low concentration can even act as nanonutrition for barley growth ^[36][159]. Bared and oxidizing Fe₃O₄ NPs of ~7 nm (96 h, 3300 mg/L) were proven to not be ecotoxic to plants, while the addition of humic acids or oxidization will increase the inhibitory effect on their unicellular ciliates ^[37][160]. Halloysite nanotubes supporting Fe₃O₄ NPs (~10 nm, 48 h, 200 mg/L) showed no acute toxicity on freshwater organisms ^[38][161]. In the application of Fe-dissolution catalysts (activation of H₂O₂ and persulfate), the dissolved iron ions can be toxic to unicellular ciliates (24 h, 1 mg/L) and slightly toxic to white mustard (96 h, 35 mg/L) ^[37][160], while another study indicated that water samples remediated by carbon-supported Fe₃O₄ (96 h, 500 mg/L) via Fenton reaction exhibited safe effects on aquatic organisms (fish and green algae) in acute and chronic toxicity tests ^[39][162].

As Fe₃O₄ is always adopted as a support, the toxicity of the catalyst should also take the potential toxicity of the supported NPs into consideration. Most of the engineered NPs have adverse effects on living organisms, and their nanotoxicology is highly dependent on exposure dosage ^[40][41][163,164]. Therefore, despite the toxicity of some nanocatalysts, their risk of causing environmental and biological damage can be significantly reduced by magnetically recovering them from the reaction system.

Nonetheless, as the leakage of supported NPs, Fe₃O₄ NPs, and iron ions from nanocatalysts is commonly reported on in current application researches, further studies may focus on the following: (i) improving hybridization strategy to prevent leakage; (ii) developing a deeper understanding of the size, coating, shape, structure, and dosage on environmental fate and toxicity of the nanocatalyst, for the development of biocompatible and biodegradable Fe₃O₄-based catalysts.

When applied in cancer treatment, studies have shown that Fe₃O₄ NPs may cross the blood–brain barrier and pose potential cytotoxicity- and genotoxicity-related risks to healthy human cells, tissues, and organs via the generation of ROS, which may give rise to lipid peroxidation, mitochondrial dysfunction, chromosomal and DNA damage, leading to protein denaturation and altered cell cycle and gene expression ^[42][43][165,166], while the level of toxicity in Fe₃O₄ NPs depends on their size, shape, surface coating, dosage, exposure time, and type of cells ^[44][45][167,168]. Poly(acrylic acid) coating on Fe₃O₄ NPs can significantly reduce their innate toxicity of bared Fe₃O₄ NPs ^[46][169]. A study conducted by Wu et al. indicated that Fe₃O₄ NPs with a size of 8 nm and coated with polymers could inhibit tumor growth efficiently without expressing obvious toxicity ^[47][170]. A toxicity determination test for nanocomposites of reduced graphene oxide, Fe₃O₄, and poly-(ethylene) glycol by standard assay revealed over 70% cell survival after 48 h, suggesting that the synthesis of nanocomposites is feasible for magnetic hyperthermia ^[48][171]. Whilst plenty of toxicity studies have been carried out in the literature, researcheours' collective understanding of the exact fate of Fe₃O₄-based materials inside the human body in cancer treatment still remains ambiguous ^[49][172].

Therefore, it is essential to comprehensively investigate the toxicity of and potential threat to human health Fe₃O₄-based materials pose. This would involve investigating their biocompatibility, biodegradation, biodistribution, on-demand targeting release in the human body, and their fate inside human body. Further studies need to be carried out using in vivo and in vitro models, along with a systematic evaluation of the toxicity of Fe₃O₄-based materials and their potential threat to human health, while considering their size, morphology, coating, delivery route, and dosing strategy. In addition, measures and strategies to prevent or shield their toxicity for a safer use in cancer treatment are also required.