Cancer is among the leading causes of mortality globally, with nearly 10 million deaths in 2020. The emergence of nanotechnology has revolutionised treatment strategies in medicine, with rigorous research focusing on designing multi-functional nanoparticles (NPs) that are biocompatible, non-toxic, and target-specific. Iron-oxide-based NPs have been successfully employed in theranostics as imaging agents and drug delivery vehicles for anti-cancer treatment. Substituted iron-oxides (MFe2O4) have emerged as potential nanocarriers due to their unique and attractive properties such as size and magnetic tunability, ease of synthesis, and manipulatable properties. Current research explores their potential use in hyperthermia and as drug delivery vehicles for cancer therapy. Significantly, there are considerations in applying iron-oxide-based NPs for enhanced biocompatibility, biodegradability, colloidal stability, lowered toxicity, and more efficient and targeted delivery. This review covers iron-oxide-based NPs in cancer therapy, focusing on recent research advances in the use of ferrites. Methods for the synthesis of cubic spinel ferrites and the requirements for their considerations as potential nanocarriers in cancer therapy are discussed. The review highlights surface modifications, where functionalisation with specific biomolecules can deliver better efficiency. Finally, the challenges and solutions for the use of ferrites in cancer therapy are summarised.
Cancer-based magnetic theranostics has gained significant interest in recent years and can contribute as an influential archetype in the effective treatment of cancer. Owing to their excellent biocompatibility, minute sizes and reactive functional surface groups, magnetic nanoparticles (MNPs) are being explored as potential drug delivery systems. In this study, MgFe2O4 ferrite MNPs were evaluated for their potential to augment the delivery of the anticancer drug doxorubicin (DOX). These MNPs were successfully synthesized by the glycol-thermal method and functionalized with the polymers; chitosan (CHI), polyvinyl alcohol (PVA) and polyethylene glycol (PEG), respectively, as confirmed by Fourier transform infrared (FTIR) spectroscopy. X-ray diffraction (XRD) confirmed the formation of the single-phase cubic spinel structures while vibrating sample magnetometer (VSM) analysis confirmed the superparamagnetic properties of all MNPs. Transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA) revealed small, compact structures with good colloidal stability. CHI-MNPs had the highest DOX encapsulation (84.28%), with the PVA-MNPs recording the lowest encapsulation efficiency (59.49%). The 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyl tetrazolium bromide (MTT) cytotoxicity assays conducted in the human embryonic kidney (HEK293), colorectal adenocarcinoma (Caco-2), and breast adenocarcinoma (SKBR-3) cell lines showed that all the drug-free polymerized MNPs promoted cell survival, while the DOX loaded MNPs significantly reduced cell viability in a dose-dependent manner. The DOX-CHI-MNPs possessed superior anticancer activity (<40% cell viability), with approximately 85.86% of the drug released after 72 h in a pH-responsive manner. These MNPs have shown good potential in enhancing drug delivery, thus warranting further optimizations and investigations.
Magnetic nanoparticles (MNPs) have been widely investigated as a strategy to improve the delivery efficiency of therapeutic and diagnostic agents. Substituted iron oxides or ferrite nanoparticles (NPs) such as CoFe2O4 represent an interesting and novel class of MNPs, although they are under-researched in the field of biomedicine. In this study, chitosan-functionalized Mg0.5Co0.5Fe2O4 NPs were loaded with the anti-cancer 5-fluorouracil (5-FU) drug to yield CS-Mg0.5Co0.5Fe2O4-5FU. Transmission electron microscopy (TEM), Fourier Transform infra-red (FTIR) spectroscopy and nanoparticle tracking analysis (NTA) were employed to determine the physiochemical properties of the NPs. Physico-chemical characterizations confirmed spherical NPs with particle sizes of approximately 20.39 nm. Improved colloidal stability was observed, as determined by a zeta potential of approximately −20 mV for the drug-loaded CS-Mg0.5Co0.5Fe2O4 NPs. Drug encapsulation efficiencies of >60% were attained, showing a pH-dependent release of 5-FU. Cell viabilities investigated using the 3-[(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] (MTT) and sulforodhamine B (SRB) assays in human embryonic kidney (HEK293), human breast adenocarcinoma (MCF-7) and human cervical cancer (HeLa) cells showed that these drug-loaded NPs exhibited more targeted tumor-specific cytotoxicities compared to free drugs. CS-Mg0.5Co0.5Fe2O4-5-FU NPs displayed significant targeted delivery potential to the investigated cancer cell lines. Conclusively, these results suggest that the CS-Mg0.5Co0.5Fe2O4-5-FU NPs are promising therapeutic delivery systems in anti-cancer treatment.
Manganese ferrite (MnFe2O4) and manganese-cobalt ferrite (Mn0.5Co0.5Fe2O4) fine powders were produced by glycol-thermal technique. Fine powders were then milled with chitosan for different times ranging from 5 hours to 60 hours. XRD patterns of the as-prepared and milled oxides confirm cubic phase structure with an average crystallite size of 11 nm. The observed values of lattice parameter decrease with milling due to the inversion of cations induced by milling. TEM results reveal nanoparticles with spherical shape and average particle sizes correlating to XRD data. No aggregation of particles was observed after milling suggesting effective chitosan coating. Magnetization studies performed at room temperature in fields up to 14 kOe revealed the superparamagnetic nature of both naked and coated nanoparticles with spontaneous and saturation magnetizations decreasing with milling. Larger coercive fields observed in Mn-Co oxides were attributed to higher magnetic anisotropy associated with Co ions. A reduction of coercive field due to milling duration was observed. 57Fe Mössbauer spectra of Mn0.5Co0.5Fe2O4 samples show ordered magnetic states, while paramagnetic nature is revealed in MnFe2O4 samples. Hence, current results suggest that chitosan coating can be successfully achieved through mechanical milling resulting in nanoparticles with potential for biomedical applications. The differences in the magnetic properties of the samples are discussed based on Stoner-Wohlfarth theory.
We report the influence of polymer coatings on structural and magnetic properties of MnFe2O4 and Mn0.5Co0.5Fe2O4 nanoferrites synthesized by glycol thermal technique and then coated with chitosan viz. CHI-MnFe2O4 and CHI-Mn0.5Co0.5Fe2O4. The compounds were characterized by X-ray diffraction (XRD), high-resolution transmission electron microscopy (HRTEM), high-resolution scanning electron microscopy (HRSEM), Mössbauer spectroscopy and magnetization measurements. The powder XRD patterns of naked nanoferrites confirmed single-phase spinel cubic structure with an average crystallite size of 13 nm, while the coated samples exhibited an average particle size of 15 nm. We observed a reduction in lattice parameters with coating. HRTEM results correlated well with XRD results. 57Fe Mössbauer spectra showed ordered magnetic spin states in both nanoferrites. This study shows that coatings have significant effects on the structural and magnetic properties of Mn-nanoferrites. Magnetization studies performed at room temperature in fields up to 14 kOe revealed the superparamagnetic nature of both naked and coated nanoparticles with spontaneous magnetizations at room temperature of 49.2 emu/g for MnFe2O4, 23.6 emu/g for coated CHI–MnFe2O4 nanoparticles, 63.2 emu/g for Mn0.5Co0.5Fe2O4 and 33.2 emu/g for coated CHI–Mn0.5Co0.5Fe2O4 nanoparticles. We observed reduction in coercive fields due to coating. Overall, chitosan-coated manganese and manganese-cobalt nanoferrites present as suitable candidates for biomedical applications owing to physicochemical, and magnetic properties exhibited.
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