Synthesis and Cytotoxicity Assessment of Citrate-Coated Calcium and Manganese Ferrite Nanoparticles for Magnetic Hyperthermia

Calcium-doped manganese ferrite nanoparticles (NPs) are gaining special interest in the biomedical field due to their lower cytotoxicity compared with other ferrites, and the fact that they have improved magnetic properties. Magnetic hyperthermia (MH) is an alternative cancer treatment, in which magnetic nanoparticles promote local heating that can lead to the apoptosis of cancer cells. In this work, manganese/calcium ferrite NPs coated with citrate (CaxMn1−xFe2O4 (x = 0, 0.2, 1), were synthesized by the sol-gel method, followed by calcination, and then characterized regarding their crystalline structure (by X-ray diffraction, XRD), size and shape (by Transmission Electron Microscopy, TEM), hydrodynamic size and zeta potential (by Dynamic Light Scattering, DLS), and heating efficiency (measuring the Specific Absorption Rate, SAR, and Intrinsic Loss Power, ILP) under an alternating magnetic field. The obtained NPs showed a particle size within the range of 10 nm to 20 nm (by TEM) with a spherical or cubic shape. Ca0.2Mn0.8Fe2O4 NPs exhibited the highest SAR value of 36.3 W/g at the lowest field frequency tested, and achieved a temperature variation of ~7 °C in 120 s, meaning that these NPs are suitable magnetic hyperthermia agents. In vitro cellular internalization and cytotoxicity experiments, performed using the human cell line HEK 293T, confirmed cytocompatibility over 0–250 µg/mL range and successful internalization after 24 h. Based on these studies, our data suggest that these manganese-calcium ferrite NPs have potential for MH application and further use in in vivo systems.

[1]  F. Dousti,et al.  Novel MR imaging nanoprobe for hepatocellular carcinoma detection based on manganese–zinc ferrite nanoparticles: in vitro and in vivo assessments , 2022, Journal of Cancer Research and Clinical Oncology.

[2]  Eue-Soon Jang,et al.  Investigation on the physico-chemical properties, hyperthermia and cytotoxicity study of magnesium doped manganese ferrite nanoparticles , 2022, Materials Chemistry and Physics.

[3]  Eue-Soon Jang,et al.  Ca-Doped MgFe2O4 Nanoparticles for Magnetic Hyperthermia and Their Cytotoxicity in Normal and Cancer Cell Lines , 2022, ACS Applied Nano Materials.

[4]  L. Hilliou,et al.  Tuning the drug multimodal release through a co-assembly strategy based on magnetic gels. , 2022, Nanoscale.

[5]  R. Ivkov,et al.  Clinical magnetic hyperthermia requires integrated magnetic particle imaging , 2022, Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology.

[6]  M. Shobana,et al.  Role of Ferrite Nanoparticles in Hyperthermia Applications , 2022, Journal of Magnetism and Magnetic Materials.

[7]  E. Naderi,et al.  Evaluation of physical properties, cytotoxicity, and antibacterial activities of calcium–cadmium ferrite nanoparticles , 2022, Applied Physics A.

[8]  B. Almeida,et al.  Development of Thermo- and pH-Sensitive Liposomal Magnetic Carriers for New Potential Antitumor Thienopyridine Derivatives , 2022, Materials.

[9]  T. Pellegrino,et al.  Magnetic nanoparticles and clusters for magnetic hyperthermia: optimizing their heat performance and developing combinatorial therapies to tackle cancer. , 2021, Chemical Society reviews.

[10]  N. Akhlaghi,et al.  Manganese ferrite (MnFe2O4) Nanoparticles: From synthesis to application -A review , 2021 .

[11]  Ruby Gupta,et al.  Effect of manganese doping on the hyperthermic profile of ferrite nanoparticles using response surface methodology , 2021, RSC advances.

[12]  L. Hilliou,et al.  Impact of Citrate and Lipid-Functionalized Magnetic Nanoparticles in Dehydropeptide Supramolecular Magnetogels: Properties, Design and Drug Release , 2020, Nanomaterials.

[13]  Raluca M. Fratila,et al.  Intracellular number of magnetic nanoparticles modulates the apoptotic death pathway after magnetic hyperthermia treatment. , 2020, ACS applied materials & interfaces.

[14]  M. Nazir,et al.  Synthesis, morphological and electromagnetic evaluations of Ca doped Mn spinel nanoferrites for GHz regime applications , 2020 .

[15]  B. Espiña,et al.  Magnetic Hyperthermia for Cancer Treatment: Main Parameters Affecting the Outcome of In Vitro and In Vivo Studies , 2020, Molecules.

[16]  I. Hilger,et al.  Hyperthermia affects collagen fiber architecture and induces apoptosis in pancreatic and fibroblast tumor hetero-spheroids in vitro. , 2020, Nanomedicine : nanotechnology, biology, and medicine.

[17]  P. Taboada,et al.  Cubic anisotropic Co and Zn substituted ferrite nanoparticles as multimodal magnetic agents. , 2020, ACS applied materials & interfaces.

[18]  A. Azizi,et al.  Synthesis and characterization of manganese ferrite nanostructure by co-precipitation, sol-gel, and hydrothermal methods , 2019 .

[19]  E. Páll,et al.  Hyperthermia, Cytotoxicity, and Cellular Uptake Properties of Manganese and Zinc Ferrite Magnetic Nanoparticles Synthesized by a Polyol-Mediated Process , 2019, Nanomaterials.

[20]  G. Ciofani,et al.  Innovative approaches for cancer treatment: current perspectives and new challenges , 2019, Ecancermedicalscience.

[21]  Yun-Ming Wang,et al.  Superparamagnetic iron oxide nanoparticulate system: synthesis, targeting, drug delivery and therapy in cancer. , 2019, Dalton transactions.

[22]  G. Dini,et al.  Polyethylene glycol-coated manganese-ferrite nanoparticles as contrast agents for magnetic resonance imaging , 2019, Journal of Magnetism and Magnetic Materials.

[23]  M. R. Mozafari,et al.  Impact of Particle Size and Polydispersity Index on the Clinical Applications of Lipidic Nanocarrier Systems , 2018, Pharmaceutics.

[24]  Zhigang Wang,et al.  Intermittent time-set technique controlling the temperature of magnetic-hyperthermia-ablation for tumor therapy , 2018, RSC advances.

[25]  A. Srinivasan,et al.  Structural and magnetic properties of sol-gel derived CaFe 2 O 4 nanoparticles , 2018 .

[26]  P. Raji,et al.  Structural and magnetic properties of calcium doped nickel ferrite nanoparticles by co-precipitation method , 2017 .

[27]  B. Majlis,et al.  Influence of calcination temperatures on structure and magnetic properties of calcium ferrite nanoparticles synthesized via sol-gel method , 2017 .

[28]  I. Rhee,et al.  Magnetic heating of silica-coated manganese ferrite nanoparticles , 2016 .

[29]  L. Paz-Ares,et al.  Current Challenges in Cancer Treatment. , 2016, Clinical therapeutics.

[30]  Junghwan Oh,et al.  In vitro study on apoptotic cell death by effective magnetic hyperthermia with chitosan-coated MnFe2O4 , 2016, Nanotechnology.

[31]  Dipak Maity,et al.  Recent advances in superparamagnetic iron oxide nanoparticles (SPIONs) for in vitro and in vivo cancer nanotheranostics. , 2015, International journal of pharmaceutics.

[32]  M. Morales,et al.  Hydrothermal synthesis of fine stabilized superparamagnetic nanoparticles of Zn2+ substituted manganese ferrite , 2015 .

[33]  N. H. Sulaiman,et al.  Superparamagnetic calcium ferrite nanoparticles synthesized using a simple sol-gel method for targeted drug delivery. , 2015, Bio-medical materials and engineering.

[34]  D. Sakellari,et al.  In vitro application of Mn-ferrite nanoparticles as novel magnetic hyperthermia agents. , 2014, Journal of materials chemistry. B.

[35]  Mustapha Sadki,et al.  The HighScore suite , 2014, Powder Diffraction.

[36]  Sujan Dutta,et al.  Biocompatible mesoporous silica-coated superparamagnetic manganese ferrite nanoparticles for targeted drug delivery and MR imaging applications. , 2014, Journal of colloid and interface science.

[37]  K. Bamzai,et al.  Preparation, and Structural and Magnetic Properties of Ca Substituted Magnesium Ferrite with Composition MgCaxFe2−xO4 ( = 0.00, 0.01, 0.03, 0.05, 0.07) , 2014 .

[38]  C. Cremisini,et al.  Biodistribution and acute toxicity of a nanofluid containing manganese iron oxide nanoparticles produced by a mechanochemical process , 2014, International journal of nanomedicine.

[39]  O. Caltun,et al.  Synthesis and characterizations of manganese ferrites for hyperthermia applications , 2013 .

[40]  N. Verma,et al.  Synthesis, characterization and in vitro cytotoxicity study of calcium ferrite nanoparticles , 2013 .

[41]  H. Mamiya.  Recent Advances in Understanding Magnetic Nanoparticles in AC Magnetic Fields and Optimal Design for Targeted Hyperthermia , 2013 .

[42]  Mojca Pavlin,et al.  Visualization of internalization of functionalized cobalt ferrite nanoparticles and their intracellular fate , 2013, International journal of nanomedicine.

[43]  Yuan-xin Wu,et al.  Sol-Gel synthesized magnetic MnFe 2 O 4 spinel ferrite nanoparticles as novel catalyst for oxidative degradation of methyl orange , 2013 .

[44]  Peng Wang,et al.  Natural and engineered nano and colloidal transport: role of zeta potential in prediction of particle deposition. , 2009, Langmuir : the ACS journal of surfaces and colloids.

[45]  L. Alexander,et al.  Determination of Crystallite Size with the X‐Ray Spectrometer , 1950 .