Synthesis and Optimization of MoS2@Fe3O4-ICG/Pt(IV) Nanoflowers for MR/IR/PA Bioimaging and Combined PTT/PDT/Chemotherapy Triggered by 808 nm Laser

Abstract

Elaborately designed biocompatible nanoplatforms simultaneously achieving multimodal bioimaging and therapeutic functions are highly desirable for modern biomedical applications. Herein, uniform MoS₂ nanoflowers with a broad size range of 80-180 nm have been synthesized through a facile, controllable, and scalable hydrothermal method. The strong absorbance of MoS₂ nanoflowers at 808 nm imparts them with high efficiency and stability of photothermal conversion. Then a novel multifunctional composite of MoS₂@Fe₃O₄-ICG/Pt(IV) (labeled as Mo@Fe-ICG/Pt) is designed by covalently grafting Fe₃O₄ nanoparticles with polyethylenimine (PEI) functionalized MoS₂, and then loading indocyanine green molecules (ICG, photosensitizers) and platinum (IV) prodrugs (labeled as Pt(IV) prodrugs) on the surface of MoS₂@Fe₃O₄. The resulting Mo@Fe-ICG/Pt nanocomposites can achieve excellent magnetic resonance/infrared thermal/photoacoustic trimodal biomaging as well as remarkably enhanced antitumor efficacy of combined photothermal therapy, photodynamic therapy, and chemotherapy triggered by a single 808 nm NIR laser, thus leading to an ideal nanoplatform for cancer diagnosis and treatment in future.

Keywords: 808 nm; MoS2 nanoflowers; bioimaging; combined therapy; size control.

Figure 1

a) A scheme showing the preparation process of Mo@Fe‐ICG/Pt nanocomposites. b) SEM image of MoS₂ nanoflowers. TEM images of c) MoS₂, d) MoS₂‐PEI, and e) MoS₂@Fe₃O₄. f) The XRD of MoS₂ nanoflowers. g) The UV–vis–NIR absorption spectra of Fe₃O₄, ICG, MoS₂‐PEI, MoS₂@Fe₃O₄, and Mo@Fe‐ICG. h) Photos of Mo@Fe‐ICG aqueous solution (0.2 × 10⁻³ m of Mo) before (left) and after (right) standing for 48 h.

Figure 2

a) The UV–vis–NIR absorption spectra of different concentrations of Mo@Fe‐ICG. b) Temperature variation curves of Mo@Fe‐ICG solutions with different concentrations of Mo under 808 nm (0.65 W cm⁻²). c) Temperature variation curve of Mo@Fe‐ICG (0.8 × 10⁻³ m) under 808 nm (0.65 W cm⁻²). The laser was turned off after irradiation for 8 min. d) Plot of cooling time versus negative natural logarithm of the temperature driving force. The time constant is calculated to be τ_s = 201 s.

Figure 3

a) Absorption spectra of DPBF solution incubated with Mo@Fe‐ICG (100 × 10⁻⁶ m of Mo) under 808 nm irradiation for different times. b) Absorption variation trends of DPBF solutions incubated with MoS₂@Fe₃O₄ and Mo@Fe‐ICG (100 × 10⁻⁶ m of Mo) respectively as a functional of 808 nm radiation time. Intracellular ROS detection treated with c) Control, d) MoS₂@Fe₃O₄, and e) Mo@Fe‐ICG (100 × 10⁻⁶ m of Mo) after the 808 nm laser irradiation (1.0 W cm⁻², 5 min).

Figure 4

The UV–vis–NIR absorption spectra of a) free ICG, b) MoS₂@Fe₃O₄, and c) Mo@Fe‐ICG aqueous solutions irradiated with 808 nm (0.65 W cm⁻²) for different times. Insets in (a) and (c) are the photos before (left) and after (right) the irradiation. d) The absorption intensity changes (at 808 nm) of MoS₂@Fe₃O₄, Pure ICG, and Mo@Fe‐ICG aqueous solutions as a function of radiation time.

Figure 5

a₁) In vitro T ₂ weight MR images of Mo@Fe‐ICG at different Fe concentrations. a₂) Relaxation rate R ₂ (1/T ₂) versus different molar Fe concentrations. T ₂‐weighted MR images of a tumor‐bearing Balb/c mouse: a₃) preinjection and a₄) after injection of Mo@Fe‐ICG (2 × 10⁻³ m of Mo, 200 µL). b) Infrared thermal images of tumor‐bearing Balb/c mice injected with saline (as control group) or Mo@Fe‐ICG solutions (2 × 10⁻³ m of Mo, 200 µL) under 808 nm laser. c) The correlations between the PA values and the corresponding concentrations of MoS₂@Fe₃O₄ and Mo@Fe‐ICG. The in vivo PA imagings of the tumor‐bearing mice d) before and e) after the injection of Mo@Fe‐ICG (2 × 10⁻³ m of Mo, 200 µL).

Figure 6

a) In vitro cytotoxicity of Mo@Fe‐ICG against L929 cells after 24 h incubation. b) Flow cytometry analysis of Hela cells under different 808 nm NIR irradiation power densities (b₁: 0 W cm⁻²; b₂: 0.5 W cm⁻²; b₃: 1.0 W cm⁻²) after incubated with Mo@Fe‐ICG/Pt (100 × 10⁻⁶ m of Mo). c) In vitro cytotoxicity of MoS₂@Fe₃O₄, MoS₂@Fe₃O₄+NIR, Mo@Fe‐ICG, Mo@Fe‐ICG+NIR, Mo@Fe‐ICG/Pt, and Mo@Fe‐ICG/Pt+NIR against HeLa cell after 24 h incubation. The cells were either exposed to 808 nm laser (1.0 W cm⁻²) for 5 min or not. d) JC‐1 probes were used as the mitochondrial membrane potential indicator through comparing the fluorescence intensity ratio of red and green. The incubation concentration of Mo@Fe‐ICG/Pt is 100 × 10⁻⁶ m and the 808 nm NIR irradiation power density is 1.0 W cm⁻².

Figure 7

a) The body weights and b) the relative tumor volumes of Balb/c mice after various intratumor treatments. The mice were intratumorally injected with 2 × 10⁻³ m of nanomaterials and received 808 nm irradiation (1.5 W cm⁻², 10 min) 6 h after the injection. c) Representative photographs of mice after different intratumoral treatments. d) The photographs and the mean tumor weights of the excised tumors after various treatments. e) Hematoxylin and eosin (H&E) staining of tumor slices for control, NIR, Mo@Fe‐ICG/Pt, and Mo@Fe‐ICG/Pt+NIR groups, respectively.

Figure 8

a) The body weights and b) the relative tumor volumes of Balb/c mice after various tail‐vein injection treatments. c) Representative photographs of mice after different tail‐vein injection treatments. d) Hematoxylin and eosin (H&E) staining of tumor slices for NIR‐2, Mo@Fe‐ICG/Pt, Mo@Fe‐ICG/Pt+NIR‐1, and Mo@Fe‐ICG/Pt+NIR‐2 groups, respectively. The injection concentration is 2 × 10⁻³ m of Mo, and the NIR‐1 and NIR‐2 represent 808 nm laser with a power density of 1.5 and 2.5 W cm⁻², respectively.

Figure 9

a–d) Serum biochemistry data including alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), creatinine (CRE), and creatine kinase (CK). e) H&E staining images of the representative main organ slices, such as the heart, liver, spleen, lung, and kidney after the tail‐vein injection of Mo@Fe‐ICG (2 × 10⁻³ m of Mo).

Figure 10

The in vivo biodistribution of Mo element after injecting Mo@Fe‐ICG nanocomposites (2 × 10⁻³ m of Mo) intravenously at different time points.