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. 2021 Feb 5;14(2):124.
doi: 10.3390/ph14020124.

Highly Efficient T2 Cobalt Ferrite Nanoparticles Vectorized for Internalization in Cancer Cells

Eva Mazarío  1 , Magdalena Cañete  2 , Fernando Herranz  3 , Jorge Sánchez-Marcos  1 , Jesús M de la Fuente  4   5 , Pilar Herrasti  1 , Nieves Menéndez  1
Affiliations

Highly Efficient T2 Cobalt Ferrite Nanoparticles Vectorized for Internalization in Cancer Cells

Eva Mazarío et al. Pharmaceuticals (Basel). .

Abstract

Uniform cobalt ferrite nanoparticles have been synthesized using an electrochemical synthesis method in aqueous media. Their colloidal, magnetic, and relaxometric properties have been analyzed. The novelty of this synthesis relies on the use of iron and cobalt foils as precursors, which assures the reproducibility of the iron and cobalt ratio in the structure. A stable and biocompatible targeting conjugate nanoparticle-folic acid (NP-FA) was developed that was capable of targeting FA receptor positivity in HeLa (human cervical cancer) cancer cells. The biocompatibility of NP-FA was assessed in vitro in HeLa cells using the MTT assay, and morphological analysis of the cytoskeleton was performed. A high level of NP-FA binding to HeLa cells was confirmed through qualitative in vitro targeting studies. A value of 479 Fe+Co mM-1s-1 of transverse relaxivity (r2) was obtained in colloidal suspension. In addition, in vitro analysis in HeLa cells also showed an important effect in negative T2 contrast. Therefore, the results show that NP-FA can be a potential biomaterial for use in bio medical trials, especially as a contrast agent in magnetic resonance imaging (MRI).

Keywords: cobalt ferrite; contrast agent; folic acid; internalization; nanoparticles; targeting.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
(a) Thermogravimetric analysis of bare nanoparticles (NP) (black line) and nanoparticle-folic acid (NP-FA) (blue line) under air conditions. The striped square is a guide for eyes to highlight the difference in weight loss between samples. (b) FTIR spectrum of bare NPs, NPs functionalized with folic acid, and the FA molecule.
Figure 2
Figure 2
(a) Transmission electron microscopy (TEM) images of nanoparticles functionalized with folic acid. (b) Comparison of the nanoparticle size and hydrodynamic size distribution.
Figure 3
Figure 3
(a) Magnetic hysteresis loop at 300 K, (b) zero-field-cooling/field-cooling (ZFC/FC) curves, both of them for the sample NP-FA. Magnetization (M) was reflected as emu per gram of nanoparticle.
Figure 4
Figure 4
(a) T1 and T2 inverse measurements vs. cobalt and iron millimolar concentration. The slope of these curves corresponds to r1 and r2 relaxivities. (b) T2-weigthed magnetic resonance (MR) images of NP-FA in aqueous solution at various metal concentrations using a Varian 7T micro magnetic resonance imaging (MRI) scanner.
Figure 5
Figure 5
Bars diagram of biocompatibility of NPs functionalized with folic acid in HeLa cells measured by MTT assay. Blue columns, cells incubated 6 h with different concentrations of NPs and their viability measured 24 h later. Green columns, cells incubated for 24 h and their viability measured 24 h later. The results represent the average of 6 independent experiments. Optical micrographies of control cells, NP-FA 0.6 mM internalization in HeLa cells incubated for 6 and 24 h. Scale bar 10 µm.
Figure 6
Figure 6
Analysis of cytoskeleton in HeLa cells incubated 24 h with 0.6 mM metal concentration and observed under fluorescence and bright-field microscopy immediately after incubations. (a) Immunofluorescence staining of α-tubulin observed under blue light excitation. (b) TRITC-phalloidin visualization of actin microfilaments observed under green light excitation.
Figure 7
Figure 7
MRI of phantoms were performed to measure the T2 relaxivity of the SPION complex-labeled cells. (a,b) Transversal and longitudinal T2-weighted images of HeLa cells incubated with varied concentration of NP-FA.
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