Formulation and Characterization of Poly (Ethylene Glycol)-Coated Core-Shell Methionine Magnetic Nanoparticles as a Carrier for Naproxen Delivery: Growth Inhibition of Cancer Cells

Abstract

An efficient and selective drug delivery vehicle for cancer cells can remarkably improve therapeutic approaches. In this study, we focused on the synthesis and characterization of magnetic Ni_1-xCo_xFe₂O₄ nanoparticles (NPs) coated with two layers of methionine and polyethylene glycol to increase the loading capacity and lower toxicity to serve as an efficient drug carrier. Ni_1-xCo_xFe₂O₄@Methionine@PEG NPs were synthesized by a reflux method then characterized by FTIR, XRD, FESEM, TEM, and VSM. Naproxen was used as a model drug and its loading and release in the vehicles were evaluated. The results for loading efficiency showed 1 mg of Ni_1-xCo_xFe₂O₄@Methionine@PEG NPs could load 0.51 mg of the naproxen. Interestingly, Ni_1-xCo_xFe₂O₄@Methionine@PEG showed a gradual release of the drug, achieving a time-release up to 5 days, and demonstrated that a pH 5 release of the drug was about 20% higher than Ni_1-xCo_xFe₂O₄@Methionine NPs, which could enhance the intracellular drug release following endocytosis. At pH 7.4, the release of the drug was slower than Ni_1-xCo_xFe₂O₄@Methionine NPs; demonstrating the potential to minimize the adverse effects of anticancer drugs on normal tissues. Moreover, naproxen loaded onto the Ni_1-xCo_xFe₂O₄@Methionine@PEG NPs for breast cancer cell lines MDA-MB-231 and MCF-7 showed more significant cell death than the free drug, which was measured by an MTT assay. When comparing both cancer cells, we demonstrated that naproxen loaded onto the Ni_1-xCo_xFe₂O₄@Methionine@PEG NPs exhibited greater cell death effects on the MCF-7 cells compared with the MDA-MB-231 cells. The results of the hemolysis test also showed good hemocompatibility. The results indicated that the prepared magnetic nanocarrier could be suitable for controlled anticancer drug delivery.

Keywords: MTT assay; Ni1−xCoxFe2O4 NPs; PEGylating; cell line; drug delivery; methionine.

Figure 1

XRD patterns for the as-prepared magnetite Ni_1−xCo_xFe₂O₄ NPs (a), methionine-coated Ni_1−xCo_xFe₂O₄ NPs (b), and Ni_1−xCo_xFe₂O₄@Methionine@PEG NPs (c).

Figure 2

The FTIR spectra of (a) methionine, (b) Ni_1−xCo_xFe₂O₄ NPs, (c) Ni_1−xCo_xFe₂O₄@Methionine, (d) Ni_1−xCo_xFe₂O₄@Methionine@PEG, (e) naproxen loaded onto the Ni_1−xCo_xFe₂O₄@Methionine@PEG, and (f) pure naproxen.

Figure 3

Magnetization curves for the as-synthesized (a) Ni_1−xCo_xFe₂O₄ NPs, (b) Ni_1−xCo_xFe₂O₄@Methionine NPs, and (c) Ni_1−xCo_xFe₂O₄@Methionine@PEG NPs.

Figure 4

FESEM micrographs of Ni_1−xCo_xFe₂O₄ NP (a), Ni_1−xCo_xFe₂O₄@Methionine NP (b), and Ni_1−xCo_xFe₂O₄@Methionine@PEG NP (c), and TEM images of Ni_1−xCo_xFe₂O₄ NP (d), Ni_1−xCo_xFe₂O₄@Methionine NP (e), and Ni_1−xCo_xFe₂O₄@Methionine@PEG NP (f).

Figure 5

Loading capacity curves of naproxen on the Ni_1−xCo_xFe₂O₄@Methionine NPs (a) and Ni_1−xCo_xFe₂O₄@Methionine@PEG NPs (b) at different initial concentrations of the drug.

Figure 6

Cumulative release curves of naproxen from naproxen-loaded Ni_1−xCo_xFe₂O₄@Methionine NPs at pH 5 (c) and pH 7.4 (b); Ni_1−xCo_xFe₂O₄@Methionine@PEG NPs at pH 5 (d) and pH 7.4 (a). Data are expressed as mean ± SD (n = 5).

Figure 7

The effect of free drug and drug-loaded carriers (a) Ni_1−xCo_xFe₂O₄@Methionine NPs and (b) Ni_1−xCo_xFe₂O₄@Methionine@PEG NPs on the viability of MCF-7 cells after incubation for (A) 24 h, (B) 48 h, and (C) 72 h. Data are expressed as mean ± SD (n = 5) (*** p < 0.001, ** p < 0.01, * p < 0.05).

Figure 8

The effect of free drug and drug-loaded carriers (a) Ni_1−xCo_xFe₂O₄@Methionine NPs and (b) Ni_1−xCo_xFe₂O₄@Methionine@PEG NPs on the viability of MDA-MB-231 cells after incubation for (A) 24 h, (B) 48 h, and (C) 72 h. Data are expressed as mean ± SD (n = 5) (*** p < 0.001, ** p < 0.01, * p < 0.05).

Figure 9

The effect of free drug and drug-loaded carriers (a) Ni_1−xCo_xFe₂O₄@Methionine NPs and (b) Ni_1−xCo_xFe₂O₄@Methionine@PEG NPs on the viability of normal MCF10A cells after incubation for 72 h. Data are expressed as mean ± SD (n = 5) (*** p < 0.001, * p < 0.05).

Figure 10

Hemolysis percentage of Ni_1−xCo_xFe₂O₄@Methionine@PEG NPs with a positive control at different concentrations.