## 4 Applications of Fe\({}_{3}\)O\({}_{4}\) Nanoparticles
### Biomedical Applications (Therapeutic and Diagnostic Technologies)
#### 4.1.3 Drug Delivery  
An increasingly applied solution for the efficient utilization of drugs against target pathogens with minimum doses is drug delivery. Fe\({}_{3}\)O\({}_{4}\) NPs are used as drug carriers in drug delivery applications due to the combinations of their multiple valuable properties, such as a strong magnetic response, low toxicity, biodegradability, biocompatibility, and inexpensiveness [123]. Furthermore, facile syntheses, easily functionalized surfaces foroconjugate coatings or enhanced colloidal stability, and the capability to be guided under a magnetic field make Fe\({}_{3}\)O\({}_{4}\) NPs an excellent candidate for drug delivery. In addition, the pristine magnetic properties for MRI imaging or hyperthermia of Fe\({}_{3}\)O  
Figure 9: TEM images of colloidal nanoclusters constructed from Fe\({}_{3}\)O\({}_{4}\) nanocube-coated amphiphilic copolymer poly(styrene-comaleic anhydride) to form (**a**) monomer clusters (1 nanocube), (**b**) dimers and trimers (2-3 nanocubes), and (**c**) centrosymmetric clusters (more than 4 nanocubes). (**d**) Schematic illustration of the preparation of soft colloidal nanoclusters. (**e**) SAR values for different soft colloidal nanoclusters. Reproduced with permission from ref. [117]. Copyright 2017 American Chemical Society.  
can be integrated to achieve multifunctional NPs for drug delivery. Fe3O4 nanocarriers are usually functionalized with polymers (e.g., pH-responsive polymers) to control drug release, biomolecules for targeting ligand-receptor species, and biocompatible porous shells (e.g., SiO2) for drug loading. [PERSON] et al. prepared 16 nm porous hollow Fe3O4 NPs with opening pores of 2-4 nm for cisplatin (an anticancer drug) storage and release [87]. The release rate of the anticancer drug cisplatin increased further at pH values lower than 6 due to acidic etching of the NP pores. These NPs were also coupled with Herceptin to target breast cancer cells. Poly(acrylic acid) (PAA), a pH-responsive polymer, was loaded into hollow 200 nm-diameter Fe3O4 NPs to obtain the pH-triggered and magnetic-targeted drug delivery of the anticancer drug doxorubicin [124]. Moreover, rattle-type Fe3O4@SiO2 hollow mesoporous spheres were synthesized with different sizes and different thicknesses of the mesoporous shell using carbon templates [125]. These NPs showed no toxicity up to a concentration of 150 \(\upmu\)g/mL and were able to load the anticancer drug doxorubicin hydrochloride into their hollow mesopores. Folic acid, a receptor-specific ligand for the targeted delivery of anticancer drugs, was further loaded on rattle-type Fe3O3@SiO2 hollow mesoporous spheres to achieve a combination of receptor-mediated targeting and magnetic targeting [126]. [PERSON] and coworkers introduced the ZnO interlayer as a microwave absorber, forming a novel Fe3O4@ZnO@SiO2 drug carrier that controls the release of cancer drugs upon exposure to microwave irradiation [127]. Special Janus nanocomposites with dual surface functionalization of polystyrene(e@Fe3O4@SiO2 were synthesized by [PERSON] et al. for tumor cell targeting and stimulus-induced drug release [128]. Based on these examples, Fe3O4 nanoparticles with magnetic properties, facile synthesis of hollow nanostructures, and easily functionalized surfaces are promising platforms for drug delivery applications.