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.
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.
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.
In this study, we have functionalised cobalt ferrite (CoFe2O4) nanoparticles (NPs) by doping with a natural bio-mineral magnesium (Mg) and coating with three polymers to enhance biocompatibility and feasibility for therapeutic applications. The glycol-thermal method was employed to synthesise CoFe2O4 and Mg0.5Co0.5Fe2O4 NPs. The latter NPs were functionalised with chitosan (CHI), poly-ethylene glycol (PEG) and poly-vinyl alcohol (PVA) to produce CHI-Mg0.5Co0.5Fe2O4, PEG-Mg0.5Co0.5Fe2O4 and PVA-Mg0.5Co0.5Fe2O4. The structure and morphology of NPs were characterized using transmission electron microscopy (TEM), high resolution TEM (HR-TEM), X-ray diffraction (XRD), Fourier transform infra-red (FTIR) spectroscopy and nanoparticle tracking analysis (NTA). Magnetic measurements were carried out using a vibrating sample magnetometer (VSM). XRD patterns confirmed inverse cubic spinel phase structure typical of ferrite NPs. NPs exhibited spherical shape with average size diameters of ranging between 8 nm and 11 nm. Coating increased these average size diameters up to 13 nm. Zeta potential measurements indicated low colloidal stability of the NPs which improved considerably with PEG and PVA coating. FTIR confirmed surface modifications seen in additional peaks characterised by amine and carbonyl groups for chitosan and PEG/PVA, respectively. CoFe2O4 NPs exhibited high saturation magnetisations of 73.861 emu/g. This value decreased with magnesium-doping and polymer-coating due to shielding effect. In vitro cytotoxicity analysis demonstrated significant tolerability of coated Mg0.5Co0.5Fe2O4 NPs at concentrations of 800 μg/ml in cervical cancer (HeLa) cell lines. Conclusively, these polymer-coated ferrites present feasible nanocarriers in magneto-targeted drug delivery.
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