Recent Progress Toward Imaging Application of Multifunction Sonosensitizers in Sonodynamic Therapy

Abstract

Sonodynamic therapy (SDT) is a rapidly developing non-surgical therapy that initiates sensitizers' catalytic reaction using ultrasound, showing great potential for cancer treatment due to its high safety and non-invasive nature. In addition, recent research has found that using different diagnostic and therapeutic methods in tandem can lead to better anticancer outcomes. Therefore, as essential components of SDT, sonosensitizers have been extensively explored to optimize their functions and integrate multiple medical fields. The review is based on five years of articles evaluating the combined use of SDT and imaging in treating cancer. By developing multifunctional sonosensitive particles that combine imaging and sonodynamic therapy, we have integrated diagnosis into the treatment of precision medicine applications, improving SDT cell uptake and antitumor efficacy utilizing different tumour models. This paper describes the imaging principle and the results of cellular and animal imaging of the multifunctional sonosensitizers. Efforts are made in this paper to provide data and design references for future SDT combined imaging research and clinical application development and to provide offer suggestions.

Keywords: imaging; multifunctional sonosensitizers; sonodynamic therapy; ultrasound.

Figure 1

Schematic illustration of the mechanism of sonodynamic therapy. The stable cavitation induced by ultrasonic irradiation promoted the sonosensitizer to enter the target area from the blood vessel, while the irradiation caused the sonosensitizers to produce ROS to kill tumour cells.

Figure 2

Imaging properties of Fe-TiO₂ NDs. (A) MR images of Fe-TiO₂ solutions with different concentrations and the relative T1 relaxation rates. (B) MR imaging of 4T1 tumour-bearing mice before and after injection of Fe-TiO₂ NDs for 24 h. (C) Quantification of MR signals from the tumours in (B). Reprinted with permission from Bai S, Yang N, Wang X, et al. Ultrasmall iron-doped titanium oxide nanodots for enhanced sonodynamic and chemodynamic cancer therapy. ACS Nano. 2020;14(11):15119–15130. Copyright [2020] American Chemical Society .

Figure 3

Imaging properties of CPDP NPs. (A) Ultrasound images of 2D and CEUS under different LIFU intensities and duration times. (B) 2D and CEUS images with and without LIFU irradiation. (C) The corresponding grayscale intensity (**p < 0.01, *p < 0.05, n = 3). After the H&E, PCNA, and TUNEL staining, the proliferate rate of PCNA in CPDP NPs + LIFU group was only 20.50%. The TUNEL results indicated CPDP NPs + LIFU group exhibited an obvious apoptosis index of 72.86%. Reproduced from Zhang Q, Wang W, Shen H, Tao H, Wu Y, Ma L, Yang G, Chang R, Wang J, Zhang H, Wang C, Zhang F, Qi J, Mi C. Low-Intensity Focused Ultrasound-Augmented Multifunctional Nanoparticles for Integrating Ultrasound Imaging and Synergistic Therapy of Metastatic Breast Cancer. Nanoscale Res Lett. 2021;16(1):73. To view a copy of this licence, visit https://creativecommons.org/licenses/by/4.0/.

Figure 4

Synthesis and imaging properties of APHB NPs. (A) The synthetic route of APHB. (B) FL images of the mice and (C) FL intensities of the tumour at different time points post-injection of APHB NPs. Ex vivo (D) FL images and (E) FL intensities of major organs and tumours at 48 h post-injection of APHB NPs. Approximately 90% cell death is found at the concentration of 100 μg/mL under ultrasound stimulation (0.6 W/cm, 60s).

Figure 5

Imaging properties of UPFB. (A) FL images of U14-tumour-bearing mice taken after i.v. injection of UPF and UPFB. (B) Ex vivo fluorescence images of major organs and tumours at 4 h post-injection with UPF and UPFB. (C) FL intensity of the major organs and tumours at different times. (D) T2-MRI of a tumour-bearing mouse with i.v. Injection of UPF or UPFB at different time intervals. The tumour site was labelled with a red ellipse. The high contents of UPFB without DMTU upon irradiation with the 808 nm laser and US exhibited the lowest cell viability rates (16.7%).

Figure 6

Synthesis and imaging properties of ABS-FA. (A) Schematic illustration for the synthesis of ABS-FA. (B) surgical navigation during tumour treatment. (C) CT imaging of HeLa tumour-bearing mice after injection of ABS-FA and ABS; red dotted circle: the tumour site. (D) Low-power (0.35 W/cm²) infrared thermal imaging of tumour-bearing mice at different time points. When HeLa cells underwent NIR irradiation and ultrasound treatment simultaneously, the survival rate when cultivated with ABS-FA was only 8.99%.

Figure 7

Imaging properties of IR780-NDs. (A) The US images (CEUS and B-mode) and corresponding quantitative analysis (B) of the echo intensities. (C) PA images and PA values at different concentrations. (D) CEUS and B-mode imaging before and after US irradiation. (E) Corresponding echo intensities of tumours. (F) Changes in PA signal intensities and images (G) at the tumour regions at the corresponding time points. (H) FL images of tumours in 4T1 tumour-bearing mice at different time points. (I) Ex vivo FL images of major organs and tumours dissected from mice 24 h post-injection. 91.52% of cells died in the IHG@P group. The lowest tumor volume was recorded in the IHG@P + US group (1.94-fold increase).