Enhanced antitumor activity of surface-modified iron oxide nanoparticles and an α-tocopherol derivative in a rat model of mammary gland carcinosarcoma

Figures & data

Figure 1 α-Tocopherol derivative with an isoprenoid side chain shortened to 6 carbon atoms in (A) phenolic and (B) acetate forms.

Figure 2 Transmission electron micrographs of (A) γ-Fe₂O₃ and (B) γ-Fe₂O₃@PDMA nanoparticles before and (C) after incubation in 0.1 M HCl (pH 3) at 37°C for 1 h, and (D) CuFe₂O₄ nanoparticles.

Figure 3 (A) FTIR spectra of (1) PDMA, (2) γ-Fe₂O₃@PDMA, and (3) γ-Fe₂O₃ nanoparticles. (B) TGA of (1) γ-Fe₂O₃ and (2) γ-Fe₂O₃@PDMA nanoparticles. (C) SQUID measurements of (1) γ-Fe₂O₃, (2) γ-Fe₂O₃@PDMA, and (3) CuFe₂O₄ nanoparticles.

Abbreviations: TGA, thermogravimetric analysis; SQUID, superconducting quantum interference device; PDMA, poly(N,N-dimethylacrylamide); FTIR, Fourier transform infrared.

Figure 4 In vitro Fe²⁺ release from (A) CuFe₂O₄, (B) γ-Fe₂O₃, and (C) γ-Fe₂O₃@PDMA nanoparticles in the presence of different concentrations of (♦) Toc and (■) Toc-6-OH. Nanoparticles (250 µg/mL) were incubated in a 0.9% NaCl solution and 10 mM Tris (pH 7.4) at 37°C for 24 h. Data are presented as the mean ± SE (n=5–8). *Significantly different from the absence of Toc and Toc-6-OH. ^#Significantly different from Toc.

Figure 5 In vitro lipid oxidation in the blood serum in the (1) absence or (2–4) presence of CuFe₂O₄, (5–7) γ-Fe₂O₃, and (8–10) γ-Fe₂O₃@PDMA nanoparticles incubated at 37°C for 24 h; (2, 5, 8) 4.4, (3, 6, 9) 44, and (4, 7, 10) 444 µg of particles per milliliter. Data are presented as the mean ± SE (n=5–8). *Significantly different from (1).

Abbreviations: TBARS, thiobarbituric acid reactive species; PDMA, poly(N,N-dimethylacrylamide).

Figure 6 Antitumor effect of γ-Fe₂O₃@PDMA nanoparticles on Walker-256 mammary gland carcinosarcoma in Wistar rats. From left to right: untreated rat with a tumor (control), rat with a tumor treated with intraperitoneally administered doxorubicin, and rat with a tumor treated with γ-Fe₂O₃@PDMA nanoparticles administered per os.

Abbreviation: PDMA, poly(N,N-dimethylacrylamide).

Figure 7 In vivo antitumor activity of nanoparticles on Walker-256 mammary gland carcinosarcoma in Wistar rats. (1) No treatment (control), treatment with (2) 1.5 mg of doxorubicin, (3) 25 mg of Toc-6-Ac, (4) 10 mg of CuFe₂O₄, (5) 10 mg of γ-Fe₂O₃, (6) 10 mg of γ-Fe₂O₃@PDMA, (7) 10 mg of CuFe₂O₄ + 25 mg of Toc-6-Ac, (8) 10 mg of γ-Fe₂O₃ + 25 mg of Toc-6-Ac, or (9) 10 mg of γ-Fe₂O₃@PDMA + 25 mg of Toc-6-Ac per kilogram of body weight. Data are presented as the mean ± SE (n=5–7). *Significantly different from (1) control animals; ^#significantly different from 2) animals treated with doxorubicin.

Abbreviation: PDMA, poly(N,N-dimethylacrylamide).

Figure 8 In vivo determination of hepatic function using (A) ALT, (B) AST, and (C) bilirubin analyses of the blood plasma of Wistar rats with Walker-256 mammary gland carcinosarcoma. (1) No treatment (tumor control), treatment with (2) 1.5 mg of doxorubicin, (3) 25 mg of Toc-6-Ac, (4) 10 mg of CuFe₂O₄, (5) 10 mg of γ-Fe₂O₃, (6) 10 mg of γ-Fe₂O₃@PDMA, (7) 10 mg of CuFe₂O₄ + 25 mg of Toc-6-Ac, (8) 10 mg of γ-Fe₂O₃ + 25 mg of Toc-6-Ac, or (9) 10 mg of γ-Fe₂O₃@PDMA + 25 mg of Toc-6-Ac kilogram of body weight, and (10) non-treated rats without a tumor (intact control). Data are presented as the mean ± SE (n=5–7). *Significantly different from (1) control animals; ^#significantly different from (4–6) animals treated with neat nanoparticles.

Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; PDMA, poly(N,N-dimethylacrylamide).

Figure 9 In vivo complete blood count of (A) white and (B) red blood cells in Wistar rats with Walker-256 mammary gland carcinosarcoma. (1) No treatment (control), treatment with (2) 1.5 mg of doxorubicin, (3) 25 mg of Toc-6-Ac, (4) 10 mg of CuFe₂O₄, (5) 10 mg of γ-Fe₂O₃, (6) 10 mg of γ-Fe₂O₃@PDMA, (7) 10 mg of CuFe₂O₄ + 25 mg of Toc-6-Ac, (8) 10 mg of γ-Fe₂O₃ + 25 mg of Toc-6-Ac, or (9) 10 mg of γ-Fe₂O₃@PDMA + 25 mg of Toc-6-Ac per kilogram of body weight, and (10) non-treated rats without a tumor (intact control). Data are presented as the mean ± SE (n=5–7). *Significantly different from (1) control animals.

Abbreviation: PDMA, poly(N,N-dimethylacrylamide).