Functionalized Magnetic Nanoparticles for NIR-Induced Photothermal Therapy of Potential Application in Cervical Cancer

Abstract

Photothermal therapy (PTT) holds great promise for cancer treatment with its effective ablation of solid tumors. As the essential core point, photothermal agents (PTAs) with excellent photothermal properties and good biocompatibility could help to fulfill highly efficient PTT. Herein, a novel type of nanoplatform Fe₃O₄@PDA/ICG (FPI) nanoparticle (NP) was designed and synthesized, which was composed of magnetic Fe₃O₄ and near-infrared excitable indocyanine green via encapsulation of polydopamine. The FPI NPs showed spherical structures in shape with uniform distribution and good chemical stability. Under 793 nm laser irradiation, FPI NPs could generate hyperthermia of 54.1 °C and photothermal conversion efficiency of 35.21%. The low cytotoxicity of FPI NPs was further evaluated and confirmed on HeLa cells with a high survival rate (90%). Moreover, under laser irradiation (793 nm), FPI NPs showed effective photothermal therapeutic characteristics for HeLa cells. Therefore, FPI NPs, as one of the promising PTAs, have great potential in the field of PTT for tumor treatment.

Figure 1

Morphology image of (A), (B) Fe₃O₄ structure, (C) XRD patterns of Fe₃O₄ NPs, morphology image of (D), (E) FPI structures. (F) Zeta potential of ICG, PDA, Fe₃O₄, FP, and FPI NPs.

Scheme 1. NIR-Emissive FPI NPs for Target-Assisted PTT for Cervical Cancer

Figure 2

Photothermal performance of samples under 793 nm laser irradiation at a power density of 0.33 W/cm²: (A) Temperature curves of ICG, Fe₃O₄, and FPI NPs in the aqueous dispersion (100 μg/mL) at various time points, respectively; (B) images of ICG, PDA, Fe₃O₄, and FPI NPs in the aqueous dispersion (from left to right, respectively); (C) temperature curves of FPI NP dispersions with various concentrations (20, 40, 60, 80, and 100 μg/mL); (D) NIR-thermal images for FPI NPs of different concentrations (20, 40, 60, 80, and 100 μg/mL).

Figure 3

(A) Photothermal stability of FPI NPs (100 μg/mL) during five cycles with/without laser (793 nm, 0.33 W/cm²). (B) Temperature evaluation of FPI NPs (100 μg/mL) with/without laser (793 nm, 0.33 W/cm²), and linear time versus -Lnθ data of FPI NPs (during the cooling period). (C) Images of FPI NPs before (left)/after (right) laser (100 μg/mL, 793 nm, and 0.33 W/cm²). (D) Temperature evaluation of free Fe₃O₄ (100 μg/mL) with/without laser (793 nm, 0.33 W/cm²), and linear time versus -Lnθ data of free Fe₃O₄ (during the cooling period).

Figure 4

(A) Fluorescence image of Fe₃O₄ and FPI NPs (concentration of 100 mg/mL) under the CLSM (λ_em = 800–1000 nm, λ_ex = 640 nm). (B) HeLa cell cytotoxicity viability by CCK-8 of HeLa cells after incubation with Fe₃O₄ and FPI NPs at different concentrations (0, 20, 40, 80, and 100 μg/mL); (C) HeLa cell viability of Fe₃O₄ and FPI NPs at different concentrations (0, 20, 40, 80, and 100 μg/mL), assessed on treated cells that were laser-irradiated at 0.33 W/cm² for 10 min. (D) Flow cytometry in the case of Control, Fe₃O₄ (40 μg/mL), and FPI NPs (40 μg/mL). Confocal microscopy of cells in bright field (E) HeLa cell (control), (F) after HeLa cell treatment with FPI NPs for 4 h.

Figure 5

CLSM images of the samples (40 μg/mL) in HeLa cells treated with different conditions (DMEM, Fe₃O₄, FPI, Fe₃O₄ and laser, and FPI and laser) (scale bar = 500 μm).

Figure 6

Under 793 nm NIR light irradiation (A) infrared thermal images of the mice treated with PBS and FPI NPs. (B) Temperature change curve of the subcutaneous injection site. (C) NIR fluorescence images of mice through the subcutaneous injection with PBS and FPI NPs at 2 h.