## 4 Applications of Fe\({}_{3}\)O\({}_{4}\) Nanoparticles
### Biomedical Applications (Therapeutic and Diagnostic Technologies)
#### 4.1.4 Multifunctional Nanoparticles in Biomedical Applications  
The potential of applying Fe3O4 NPs in biomedical applications is not limited to single functional agents, such as contrast agents, heating agents (hyperthermalia), or drug carrier nanospecies. Surface functionalization and core-shell structures of Fe3O4 NPs achieve multifunctional nanoagents with maximal activity in biomedical applications that integrate both therapeutic and diagnostic technologies in an Fe3O4 NP-based system. For example, MRI contrast agents and hyperthermia agents based on Fe3O4 nanostructures have also been used for drug delivery or integrated with biological substances and fluorescent molecules to enhance functionality in disease treatment and imaging. Immobilization of human tissue plasminogen activator (tPA) and bovine serum albumin on a cluster of multiple 20 nm Fe3O4 nanocubes was reported by [PERSON] et al. for the preparation of multifunctional thrombol and MRI contrast nanogents [129]. These nanoagents exhibited excellent thrombol activity and can potentially be applied for imaging vascular thrombi. The dissolution rate of clots was increased approximately 100-fold compared to free tPA due to the intimate interaction of tPA with the fibrin network and achieved an additional 10-fold increase through localized heating upon exposure to an alternating magnetic field. [PERSON] and coworkers synthesized Fe3O4@SiO2 core-shell nanoparticles integrated with phosphorescent iridium complexes for three-in-one purposes of MRI, luminescence imaging, and photodynamic therapy [130]. Highly uniform superparamagnetic Fe3O4 NPs with an average size of 12 nm were coated with porous, biocompatible SiO2 shells before the iridium complexes were incorporated into the SiO2 matrix. Phosphorescent iridium complexes serve as dual functional agents, including photosensizers, to generate singlet oxygen (1O2) for inducing cancer cell apoptosis and as luminescence agents for luminescence imaging. In a recent study aiming to prepare a dual-modality magnetic resonance and fluorescence unified imaging platform performed by [PERSON] and colleagues [131], lipid-encapsulated Fe3O4 NPs were combined with dialkylcarboxylate dyes before being integrated with surface peptide bioconjugation. The nanoprobes were used for stable, high-contrast MRI scans, near-infrared fluorescence imaging, and fluorescence microscopy. A novel magnetic nanocatalyst constructed from glucose oxidase (GOD)-loaded Fe3O4 hollow NPs as starvation-chemodynamic-hyperthermia synergistic therapy for tumors was reported by [PERSON] et al. [89]. Figure 10 illustrates the working principle of the nanocatalysts. Ferrous cations generate the reactive oxygen species (ROS) OH radicals from H\({}_{2}\)O\({}_{2}\) via the Fenton reaction and subsequently induce cell apoptosis by chemodynamic therapy. GOD consumes glucose, which is an important nutrient in tumor tissues, resulting in tumor tissue starvation during therapy and the generation of an excess amount of H\({}_{2}\)O\({}_{2}\) to further enhance the Fenton reaction in terms of chemodynamic activity. Moreover, GOD-loaded hollow Fe\({}_{3}\)O\({}_{4}\) NPs can be heated under an AMF for hyperthermia treatment. In addition to utilizing Fe\({}_{3}\)O\({}_{4}\) nanoparticles as the main core for further functionalization purposes, active MRI and hyperthermic Fe\({}_{3}\)O\({}_{4}\) NPs have been grafted onto the surface of Er\({}^{3+}\)/Yb\({}^{3+}\)-doped NaYF4@SiO2@AuNP core-shell nanoparticles to obtain near-infrared and magnetic-responsive nanocomposites for hyperthermia treatment [132]. Combining an active optical heater Er\({}^{3+}\)/Yb\({}^{3+}\)-doped YPO\({}_{4}\) nanophosphor with magnetic hyperthermia Fe\({}_{3}\)O\({}_{4}\) agents into a hybrid material Er\({}^{3+}\)/Yb\({}^{3+}\)-doped YPO\({}_{4}\)@Fe\({}_{3}\)O\({}_{4}\) enhances the hyperthermic activity and ability to recover the material [133].