Multifunctional Bi2S3-Au nanoclusters for fluorescence/infrared thermal imaging guided photothermal therapy

Abstract

Nanotechnology has attracted extensive attention in the diagnosis and treatment of cancer. Therefore, the research aimed at developing new nanomaterials and exploring their applications in biomedicine has attracted more attention. In this study, Bi₂S₃-Au nanoclusters (Bi₂S₃-AuNCs) as fluorescence/infrared thermal imaging-guided photothermal therapy (PTT) was prepared for the first time. It was achieved in a facile and mild way by optimizing the amount of Bi³⁺ and Au³⁺ using bovine serum albumin (BSA) as reducer and stabilizer. The as-prepared Bi₂S₃-AuNCs with special morphology showed high stability, excellent biocompatibility and good photostability. Apart from these, it also can accumulate at tumor sites and exhibit considerable fluorescence/infrared thermal imaging-guided PTT. Bi₂S₃-AuNCs nanoparticles integrate imaging and therapeutic functions into an advanced application platform, which provides the possibility to build a novel nano-cancer diagnosis and treatment platform.

Keywords: Bi2S3-Au nanoclusters; Fluorescence imaging; Infrared thermal imaging; Multifunctional; Photothermal therapy.

Graphical abstract

Scheme 1

Schematic illustration of the design process of Bi₂S₃-AuNCs.

Fig. 1

STEM-EDS element mapping (A) Bright Filed; (B) High-Angle Annular Dark Field; (C) Au element; (D) Bi element) of Bi₂S₃-AuNCs. (E) XRD image of Bi₂S₃-AuNCs (JCPDS No.79–2384 is the standard card of Bi₂S₃, JCPDS No.89–3697 is the standard card of Au). (F) full scan XPS survey spectrum of Bi₂S₃-AuNCs.

Fig. 2

(A) UV–vis spectrua of different concentrations of Bi₂S₃-AuNCs (Insert is the linear fitting curve of concentrations-808 nm absorption values of Bi₂S₃-AuNCs). - (B) UV–vis spectra of Bi₂S₃-AuNCs dissolved in different solvents (H₂O，PBS, DMEM) (Insert is the electronic pictures of Bi₂S₃-AuNCs dissolved in different solvents). Photos of lyophilized solid and solution of Bi₂S₃-AuNCs in day light (C) and and under 365 nm light (D) (The solutions from left to right are Bi₂S₃-AuNCs prepared with 0, 0.25 mg, 0.5 mg, 1.0 mg, 1.25 mg and 1.5 mg of Bi(NO₃)₃·5H₂O, respectively). (E) Emission spectra (λ_em = 670 nm) of different concenetrations of Bi₂S₃-AuNCs. (F) Linear fitting curve of concentrations-fluorescence intensities of Bi₂S₃-AuNCs.

Fig. 3

Temperature elevation curves of Bi₂S₃-AuNCs (A) at various concentrations (C_Bi = 0, 0.25, 0.50, 1.00, 2.00 and 4.0 μg/mL) under 808 nm (2 W/cm²) irradition, (B) under different power densities of 808 nm laser irradiation (C_Bi = 4.00 μg/mL). (C) Temperature elevation curves of different nanoparticles under 808 nm (2 W/cm²) irradition (4.0 μg/mL for Bi, 47 μg/mL for Au, consistent with their rations in Bi₂S₃-AuNCs); (D) the photothermal profiles of Bi₂S₃-AuNCs solution (C_Bi = 4.00 μg/mL) over five successive cycles under 808 nm (2 W/cm²) irradition. (E) Heating up and cooling curve of Bi₂S₃-AuNCs (C_Bi = 4.00 μg/mL). (F) Linear cooling time of Bi₂S₃-AuNCs and -Ln (θ).

Fig. 4

(A) Biocompatibility of Bi₂S₃, AuNCs, Bi₂S₃ + AuNCs and Bi₂S₃-AuNCs with different concentrations. (B) Biocompatibility of Bi₂S₃, AuNCs, Bi₂S₃ + AuNCs and Bi₂S₃-AuNCs with different concentrations under NIR (at 808 nm, 2 W/cm² of NIR). Cellular endocytosis of Bi₂S₃-AuNCs by B16F10 cells at varied (C) concentration (C_Bi = 1.0, 2.0 and 4.0 μg/mL, incubation for 8 h) and (D) time (1, 2 and 4 h, C_Bi = 4.0 μg/mL).

Fig. 5

(A) Infrared thermal imaging maps at different time points of tumor-bearing mice with laser irradiation (at 808 nm, 2 W/cm² of NIR) after injection of Bi₂S₃-AuNCs (Circles represent the tumor sites). (B) Temperature elevation profiles in tumor area. (C) In vivo fluorescence imaging of tumor-bearing mice at 0 h, 1 h, 4 h and 8 h after injection of Bi₂S₃-AuNCs (λ_ex = 500 nm, λ_em = 670 nm, circles represent the tumor sites).

Fig. 6

(A) Schematic illustration of the in vivo therapeutic process. (B) Photographs of tumors, (C) Tumor weights and (D) tumor relative volume after different treatments. Body weight of mice in each group (E) one week before treatment and (F) during the 12-day treatment period. (G) The body weight of mice treatment with Bi₂S₃-AuNCs+NIR group after cure. **P < 0.01, and ***P < 0.001, ns, not statistically significant.

Fig. 7

H&E staining of heart, liver, spleen, lung, and kidney tissue slices from tumor-bearing mice that received different treatments under laser (808 nm, 2 W/cm²) for 12 days (scale bar = 100 μm).