Doxorubicin/Cisplatin-Loaded Superparamagnetic Nanoparticles As A Stimuli-Responsive Co-Delivery System For Chemo-Photothermal Therapy

Figures & data

Table 1 Characteristics Of Eleven Groups For Cytotoxicity Assessment By MCF-7 Breast Cancer Cells

Group No.	Control	DOX (4.2 µg/mL)	CDDP (2.8 µg/mL)	PS-IONs (200 µg/mL)	Drug-Loaded PS-IONs	Laser
1	✓
2	✓					✓
3		✓
4		✓				✓
5			✓
6			✓			✓
7		✓	✓
8				✓
9				✓		✓
10					✓
11					✓	✓

Scheme 1 Illustration of the synthesis procedure of PS-IONs and drug loading mechanism.

Figure 1 (a, b) TEM images of PS-IONs (scale bars are 150 nm and 40 nm, respectively). (c) XRD patterns [the yellow, green, pink, blue, violet, light brown and orange squares relate to (220), (311), (400), (422), (511), (440) and (530) planes of the spinel structure of magnetite, respectively], (d) hysteresis loops, (e) FT-IR spectra, and (f) DLS particles size distribution profiles of IONs (black line) and PS-IONs (red line).

Figure 2 Viability of L929 normal fibroblast cells after 24, 48, and 72 hrs of incubation with different concentrations of PS-IONs (ranging from 10 to 500 µg/mL). There was no significant difference between the control and other groups.

Figure 3 (a) Light microscopy images of the cells (the total magnification was 400 times) exposed to 100 (left) and 200 µg/mL (right) of PS-IONs for 24 hrs. The brown dots show the uptaken nanoparticles. (b) Concentration dependent cellular uptake percentage. The inset shows the amount of PS-IONs uptake (µg/mL) versus initial PS-IONs concentration (µg/mL) in the culture media.

Table 2 Blood Coagulation Times After Dilution With The Same Volumes Of PBS And PS-IONs Suspension (final Concentration Of 200 μg/mL)

	Normal Range	Diluted With PBS	Diluted With PS-IONs (200 µg/mL)
APTT (s)	28 to 38	39.0	38.0
PT (s)	11 to 14	13.0	13.2

Figure 4 Light microscopy images (the total magnification was 400 times) of blood smear prepared samples from EDTA-anticoagulated blood without dilution (control) and after addition of PS-IONs (final concentration 200 μg/mL) and PBS after 4 h. The RBCs showed neither deformation nor aggregation when compared to the controls.

Figure 5 Loading capacity of (a) DOX and (b) CDDP on PS-IONs as a function of their initial concentation in the solutions containing 15 ppm of CDDP and DOX, respectively. In vitro release profiles of (c) DOX and (d) CDDP from PS-IONs at different temperature and pH conditions. Asterisks (*) indicate significant difference (P < 0.05).

Figure 6 (a) T₂-weighted MR images of PS-IONs in aqueous media at various concentrations and different echo times. (b) T₂ relaxation rate (R₂) versus iron concentration in PS-IONs.

Figure 7 MTT viability assay of MCF7 cells after exposure to 0.5 W/cm² near-IR laser irradiation for 10 min, incubation with 200 μg/mL of PS-IONs, chemotherapy with DOX (4.2 μg/mL) or CDDP (2.8 μg/mL), dual-drug chemotherapy, photothermal treatment, and multiple treatment method. Values are mean±SD. Double asterisks (**) indicate nonsignificant difference (P>0.05).

Table 3 Summary Of The Parameters And Outcomes Of Some SPION-Based Chemo-Photothermal Therapy Studies

Nanostructure	Concentration (µg/mL)	Laser [(W/cm^2); (λ(nm); t(min)]	Drug; Concentration (µg/mL)	Cell Line	Relaxivity (mM^−1s^−1)	Cyto-toxicity (%)	Comments
This study	200	0.5; 808; 10	DOX; 4.2 CDDP; 2.8	MCF-7	127.31	97.3 ± 0.8	–
rGO-Fe2O3@Au NPs^Citation30	50	2; 808; 5	DOX; 50	HeLa	54.99	~96	–
GO-PEG-γ-Fe2O3^Citation29	Not reported	2; 808; 5	DOX; 6	HeLa	33.15	~93	Loading factor was 1.18
Porous hollow Fe3O4^Citation23	150 µg Fe/mL	1.5; 808; 10	DOX; Not reported	4T1	119.66	~75	–
Lactobionic acid/Fe3O4@polydopamine/PEG^Citation73	125	1; 808; 30	DOX; ~46	HepG2	Not studied	75.4	Cytotoxicity increased to 83.7% after exposure to magnetic field
Fe3O4@mSiO2-PO*-folic acid^Citation26	125	2; 808; 30	DOX; ~5.6	HeLa	Not studied	81	–
Fe3O4@MnO2@PPy^Citation27	600	1; 638; 10	DOX; 420	HepG2	Not studied	91.6	Samples were placed in a magnetic field for 30 min
IONPs@AuNPs@SiNWs^Citation15	300	1; 808; 20	DOX; 50	MCF-7/ADR	Not studied	90	Samples were placed in a magnetic field for 3 hrs
Cu9S5@mSiO2@Fe3O4-PEG^Citation74	200	0.76; 980; 10	DOX; 25	HeLa	13.583	83	–
Fe3O4@MoS2/PEG/2-deoxy-D-glucose^Citation28	200	0.5; 808; 3	DOX; ~101	MDA-MB-231	48.86	~70	The cell viability decreased to 1.4% after the second treatment

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