Magnetic nanoparticles (MNPs) have great potential in various areas such as medicine, cancer therapy and diagnostics, biosensing, and material science. In particular, magnetite (Fe₃O₄) nanoparticles are extensively used for numerous bioapplications due to their biocompatibility, high saturation magnetization, chemical stability, large surface area, and easy functionalization. This paper describes magnetic nanoparticle physical and biological properties, emphasizing synthesis approaches, toxicity, and various biomedical applications, focusing on the most recent advancements in the areas of therapy, diagnostics, theranostics, magnetic separation, and biosensing.

Magnetic nanoparticles (MNPs) have great potential in biochemistry and medical science. In particular, iron oxide nanoparticles have demonstrated a promising effect in various biomedical applications due to their high magnetic properties, large surface area, stability, and easy functionalization. However, colloidal stability, biocompatibility, and potential toxicity of MNPs in physiological environments are crucial for their in vivo application. In this context, many research articles focused on the possible procedures for MNPs coating to improve their physic-chemical and biological properties. This review highlights one viable fabrication strategy of biocompatible iron oxide nanoparticles using human serum albumin (HSA). HSA is mainly a transport protein with many functions in various fundamental processes. As it is one of the most abundant plasma proteins, not a single drug in the blood passes without its strength test. It influences the stability, pharmacokinetics, and biodistribution of different drug-delivery systems by binding or forming its protein corona on the surface. The development of albumin-based drug carriers is gaining increasing importance in the targeted delivery of cancer therapy. Considering this, HSA is a highly potential candidate for nanoparticles coating and theranostics area and can provide biocompatibility, prolonged blood circulation, and possibly resolve the drug-resistance cancer problem.

Pulsed Dipolar Spectroscopy (PDS) methods of Electron Paramagnetic Resonance (EPR) were used to detect and characterize reversible non-covalent dimers of Human Serum Albumin (HSA), the most abundant protein in human plasma. The spin labels, MTSL and OX063, were attached to Cys-34 and these chemical modifications of Cys-34 did affect the dimerization of HSA, indicating that other post-translational modifications can modulate dimer formation. At physiologically relevant concentrations, HSA does form weak, non-covalent dimers with a well-defined structure. Dimer formation is readily reversible into monomers. Dimerization is very relevant to the role of HSA in the transport, binding, and other physiological processes.

Magnetic nanoparticles (MNPs) have great potential in the drug delivery area. Iron oxide (Fe₃O₄) MNPs have demonstrated a promising effect due to their ferrimagnetic properties, large surface area, stability, low cost, easy synthesis, and functionalization. Some coating procedures are required to improve stability, biocompatibility, and decrease toxicity for medical applications. Herein, the co-precipitation synthesis of iron oxide MNPs coated with four types of primary surfactants, polyethylene glycol 2000 (PEG 2000), oleic acid (OA), Tween 20 (Tw20), and Tween 80 (Tw80), were investigated. Dynamic light scattering (DLS), ζ-potential, and transmission electron microscopy (TEM) techniques were used for morphology, size, charge, and stability analysis. Methylene blue reactive oxygen species (ROS) detection assay and the toxicity experiment on the lung adenocarcinoma A549 cell line were conducted. Two loading conditions for anticancer drug doxorubicin (DOX) on MNPs were proposed. The first one provides high loading efficiency (~90%) with up to 870 μg/mg (DOX/MNPs) drug capacity. The second is perspective for extremely high capacity 1757 μg/mg with drug wasting (DOX loading efficiency ~24%). For the most perspective MNP_OA and MNP_OA_DOX in cell media, pH 7.4, 5, and 3, the stability experiments are also presented. MNP_OA_DOX shows DOX pH-dependent release in the acidic pH and effective inhibition of A549 cancer cell growth. The IC50 values were calculated as 1.13 ± 0.02 mM in terms of doxorubicin and 0.4 ± 0.03 µg/mL in terms of the amount of the nanoparticles. Considering this, the MNP_OA_DOX nano theranostics agent is a highly potential candidate for cancer treatment.

A magnetic nanocomposite (MNC) is an integrated nanoplatform that combines a set of functions of two types of materials. A successful combination can give rise to a completely new material with unique physical, chemical, and biological properties. The magnetic core of MNC provides the possibility of magnetic resonance or magnetic particle imaging, magnetic field-influenced targeted delivery, hyperthermia, and other outstanding applications. Recently, MNC gained attention for external magnetic field-guided specific delivery to cancer tissue. Further, drug loading enhancement, construction stability, and biocompatibility improvement may lead to high progress in the area. Herein, the novel method for nanoscale Fe₃O₄@CaCO₃ composites synthesis was proposed. For the procedure, oleic acid-modified Fe₃O₄ nanoparticles were coated with porous CaCO₃ using an ion coprecipitation technique. PEG-2000, Tween 20, and DMEM cell media was successfully used as a stabilization agent and template for Fe₃O₄@CaCO₃ synthesis. Transmission electron microscopy (TEM), Fourier transform infrared (FTIR) spectroscopy, and dynamic light scattering (DLS) data were used for the Fe₃O₄@CaCO₃ MNC’s characterization. To improve the nanocomposite properties, the concentration of the magnetic core was varied, yielding optimal size, polydispersity, and aggregation ability. The resulting Fe₃O₄@CaCO₃ had a size of 135 nm with narrow size distributions, which is suitable for biomedical applications. The stability experiment in various pH, cell media, and fetal bovine serum was also evaluated. The material showed low cytotoxicity and high biocompatibility. An excellent anticancer drug doxorubicin (DOX) loading of up to 1900 µg/mg (DOX/MNC) was demonstrated. The Fe₃O₄@CaCO₃/DOX displayed high stability at neutral pH and efficient acid-responsive drug release. The series of DOX-loaded Fe₃O₄@CaCO₃ MNCs indicated effective inhibition of Hela and MCF-7 cell lines, and the IC 50 values were calculated. Moreover, 1.5 μg of the DOX-loaded Fe₃O₄@CaCO₃ nanocomposite is sufficient to inhibit 50% of Hela cells, which shows a high prospect for cancer treatment. The stability experiments for DOX-loaded Fe₃O₄@CaCO₃ in human serum albumin solution indicated the drug release due to the formation of a protein corona. The presented experiment showed the “pitfalls” of DOX-loaded nanocomposites and provided step-by-step guidance on efficient, smart, anticancer nanoconstruction fabrication. Thus, the Fe₃O₄@CaCO₃ nanoplatform exhibits good performance in the cancer treatment area.