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Research Article

DMSA-Coated Cubic Iron Oxide Nanoparticles as Potential Therapeutic Agents

ORCID Icon, , ORCID Icon, ORCID Icon & ORCID Icon
Pages 925-941 | Received 15 Dec 2020, Accepted 22 Mar 2021, Published online: 21 May 2021

Figures & data

Figure 1. Transmission electron microscope images (A–C) at different magnifications and particle size distribution (D) of the decanoic acid-coated iron oxide nanoparticles synthesized by thermal decomposition method.

Scale bars for A, B and C: 20 nm, 50 nm and 10 nm, respectively.

Dmean: Mean cube edge length of the nanoparticles; SD: Standard deviation; n: Number of the nanoparticles counted.

Figure 1. Transmission electron microscope images (A–C) at different magnifications and particle size distribution (D) of the decanoic acid-coated iron oxide nanoparticles synthesized by thermal decomposition method.Scale bars for A, B and C: 20 nm, 50 nm and 10 nm, respectively.Dmean: Mean cube edge length of the nanoparticles; SD: Standard deviation; n: Number of the nanoparticles counted.
Figure 2. Transmission electron microscope images (A–C) at different magnifications, corresponding particle size distribution (D) and transmission electron microscope energy dispersive X-ray spectrum (E) of the iron oxide nanoparticles after surface functionalization with meso-2,3-dimercaptosuccinic acid.

Dmean: Mean cube edge length of the nanoparticles; SD: Standard deviation; n: Number of the nanoparticles counted.

Figure 2. Transmission electron microscope images (A–C) at different magnifications, corresponding particle size distribution (D) and transmission electron microscope energy dispersive X-ray spectrum (E) of the iron oxide nanoparticles after surface functionalization with meso-2,3-dimercaptosuccinic acid.Dmean: Mean cube edge length of the nanoparticles; SD: Standard deviation; n: Number of the nanoparticles counted.
Figure 3. Fourier transform infrared spectroscopy spectra of meso-2,3-dimercaptosuccinic acid-coated iron oxide nanoparticles (A), decanoic acid-coated iron oxide nanoparticles (B) and pure meso-2,3-dimercaptosuccinic acid (C).

DA: Decanoic acid; DMSA: Meso-2,3-dimercaptosuccinic acid; IO: Iron oxide.

Figure 3. Fourier transform infrared spectroscopy spectra of meso-2,3-dimercaptosuccinic acid-coated iron oxide nanoparticles (A), decanoic acid-coated iron oxide nanoparticles (B) and pure meso-2,3-dimercaptosuccinic acid (C).DA: Decanoic acid; DMSA: Meso-2,3-dimercaptosuccinic acid; IO: Iron oxide.
Figure 4. Thermogravimetric analysis curves (A) of iron oxide nanoparticles before (a) and after (b) meso-2,3-dimercaptosuccinic acid coating, and magnetization curves (B) of cubic iron oxide nanoparticles at room temperature before (a) and after (b) meso-2,3-dimercaptosuccinic acid coating.

DA: Decanoic acid; DMSA: Meso-2,3-dimercaptosuccinic acid; IO: Iron oxide.

Figure 4. Thermogravimetric analysis curves (A) of iron oxide nanoparticles before (a) and after (b) meso-2,3-dimercaptosuccinic acid coating, and magnetization curves (B) of cubic iron oxide nanoparticles at room temperature before (a) and after (b) meso-2,3-dimercaptosuccinic acid coating.DA: Decanoic acid; DMSA: Meso-2,3-dimercaptosuccinic acid; IO: Iron oxide.
Figure 5. Number-weighted hydrodynamic diameters of the water-dispersible iron oxide nanoparticles (A), and the zeta potentials of the water-dispersible iron oxide nanoparticles as a function of pH values (B).
Figure 5. Number-weighted hydrodynamic diameters of the water-dispersible iron oxide nanoparticles (A), and the zeta potentials of the water-dispersible iron oxide nanoparticles as a function of pH values (B).
Figure 6. Hyperthermia result of water-dispersible meso-2,3-dimercaptosuccinic acid-coated cubic iron oxide nanoparticles (IO@DMSA; 2.4 mg Fe/ml) measured in alternating magnetic field of 15.95 kA/m and frequency of 488 kHz.

(A) Temperature increase as a function of time (the red line represents the obtained data from the hyperthermia measurement, the black solid line the fit data to ΔT=ΔTm(1e) function; the blue line is the linear fit showing the initial slope of the black curve at t = 0). (B) Zoom-in view of temperature versus time curve.

Figure 6. Hyperthermia result of water-dispersible meso-2,3-dimercaptosuccinic acid-coated cubic iron oxide nanoparticles (IO@DMSA; 2.4 mg Fe/ml) measured in alternating magnetic field of 15.95 kA/m and frequency of 488 kHz.(A) Temperature increase as a function of time (the red line represents the obtained data from the hyperthermia measurement, the black solid line the fit data to ΔT=ΔTm(1−e−tτ) function; the blue line is the linear fit showing the initial slope of the black curve at t = 0). (B) Zoom-in view of temperature versus time curve.
Figure 7. Time and nanoparticle number-dependent cell viability percentages of meso-2,3-dimercaptosuccinic acid-coated iron oxide nanoparticles according to 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide assay.

All values are represented as mean ± standard deviation. *p < 0.05; **p < 0.01 and ***p < 0.001.

Figure 7. Time and nanoparticle number-dependent cell viability percentages of meso-2,3-dimercaptosuccinic acid-coated iron oxide nanoparticles according to 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide assay.All values are represented as mean ± standard deviation. *p < 0.05; **p < 0.01 and ***p < 0.001.
Figure 8. Schematic illustration of surface modified iron oxide nanoparticles with monodentate and bidentate ligand bonds.

The phase transfer reaction was performed through the reaction of DA-coated IO nanoparticles with DMSA. After ligand exchange reaction, alkalinization (or deprotonization) of DMSA with 1 M KOH solution at pH 10 was performed to enhance the stability of the nanoparticles by electrostatic repulsion between COO- groups and by increasing S–S bonds to reduce hydrodynamic size.

IO: Iron oxide; DA: Decanoic acid; DMSA: Meso-2,3-dimercaptosuccinic acid.

Figure 8. Schematic illustration of surface modified iron oxide nanoparticles with monodentate and bidentate ligand bonds.The phase transfer reaction was performed through the reaction of DA-coated IO nanoparticles with DMSA. After ligand exchange reaction, alkalinization (or deprotonization) of DMSA with 1 M KOH solution at pH 10 was performed to enhance the stability of the nanoparticles by electrostatic repulsion between COO- groups and by increasing S–S bonds to reduce hydrodynamic size.IO: Iron oxide; DA: Decanoic acid; DMSA: Meso-2,3-dimercaptosuccinic acid.
Supplemental material

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