Efficacy of iron-silver bimetallic nanoparticles to enhance radiotherapy

Abstract

Radiotherapy (RT) is one of the primary cancer treatment methods. Radiosensitizers are used to enhance RT and protect healthy tissue. Heavy metals have been studied as radiosensitizers. Thus, iron oxide and iron oxide/silver nanoparticles have been the main subjects of this investigation. A simple honey-based synthesis of iron (IONPs) and iron-silver bimetallic nanoparticles (IO@AgNPs) were prepared followed by characterization with transmission electron microscope (TEM), absorption spectra, vibrating sample magnetometer (VSM), and X-ray diffraction (XRD). Additionally, Ehrlich carcinoma was induced in 30 adult BALB/c mice and divided into 6 groups. Mice of group G1 were not treated with nanoparticles or exposed to irradiation (control group), and group G2 and G3 were treated with IONPs and IO@AgNPs respectively. Mice of group G4 were exposed to a high dose of gamma radiation (HRD) (12 Gy). Groups G5 and G6 were treated with IONPs and IO@AgNPs followed by exposure to a low dose of gamma radiation (LRD) (6 Gy) respectively. The impact of NP on the treatment protocol was evaluated by checking tumor growth, DNA damage, and level of oxidative stress in addition to investigating tumor histopathology. Additional research on the toxicity of this protocol was also evaluated by looking at the liver's cytotoxicity. When compared to HRD therapy, combination therapy (bimetallic NPs and LRD) significantly increased DNA damage by about 75% while having a stronger efficacy in slowing Ehrlich tumor growth (at the end of treatment protocol) by about 45%. Regarding the biosafety concern, mice treated with combination therapy showed lower alanine aminotransferase (ALT) levels in their liver tissues by about half the value of HRD. IO@AgNPs enhanced the therapeutic effect of low-dose radiation and increased the efficacy of treating Ehrlich tumors with the least amount of harm to normal tissues as compared to high radiation dosage therapy.

Keywords: DNA damage; Ehrlich tumor; Nanoparticles; Oxidative stress; Radiation therapy; Radiosensitizers.

Fig. 1

Transmission electron microscope (TEM) images of iron oxide nanoparticles (IONPs) and iron-silver bimetallic nanoparticles (IO@AgNPs)

Fig. 2

X-ray diffraction (XRD) of iron oxide nanoparticles (IONPs) (a) and iron-silver bimetallic nanoparticles (IO@AgNPs) (b)

Fig. 3

UV–visible spectra of iron oxide nanoparticles (IONPs) and iron-silver bimetallic nanoparticles (IO@AgNPs)

Fig. 4

Vibrating sample magnetometer (VSM) of iron oxide nanoparticles (IONPs) and iron-silver bimetallic nanoparticles (IO@AgNPs)

Fig. 5

Total antioxidant capacity (TAC) (a) and malondialdehyde (MDA) (b) levels in tumor tissue for the different groups: The control mice group (C) and mice groups treated with iron oxide nanoparticles (0.8 mg/mL) (IONPs), iron-silver nanoparticles (1.6 mg/mL) (IO@AgNPs), high radiation dose (HRD) (12 Gy), iron oxide nanoparticles (0.8 mg/mL) and low radiation dose (LRD) (6 Gy) (IONPs + 6 Gy), and iron-silver nanoparticles (1.6 mg/mL) and LRD (IO@AgNPs + 6 Gy). The nanoparticles and radiation doses were fractionated equally into 3 sessions during the treatment protocol. The data points are represented as mean ± SD (n = 5) (a, p < 0.001) compared to the control group (C) and (*, p < 0.001) compared to HRD group (12 Gy)

Fig. 6

Comet parameters observed in %DNA in tail (a), tail moment (b), and comet images (c) of tumor in all experimental groups: The control mice group (C) and mice groups treated with iron oxide nanoparticles (0.8 mg/mL) (IONPs), iron-silver nanoparticles (1.6 mg/mL) (IO@AgNPs), high radiation dose (HRD) (12 Gy), iron oxide nanoparticles (0.8 mg/mL) and low radiation dose (LRD) (6 Gy) (IONPs + 6 Gy), and iron-silver nanoparticles (1.6 mg/mL) and LRD (IO@AgNPs + 6 Gy). The nanoparticles and radiation doses were fractionated equally into 3 sessions during the treatment protocol. The data points are represented as mean ± SD (n = 5) (a, p ≤ 0.0001; b, p ≤ 0.03) compared to the control group (C) and (*, p ≤ 0.001; **, p ≤ 0.008) compared to HRD group (12 Gy)

Fig. 7

Tumor histopathology photomicrographs in control mice group (C) and mice groups treated with iron oxide nanoparticles (0.8 mg/mL) (IONPs), iron-silver nanoparticles (1.6 mg/mL) (IO@AgNPs), high radiation dose (HRD) (12 Gy), iron oxide nanoparticles (0.8 mg/mL) and low radiation dose (LRD) (6 Gy) (IONPs + 6 Gy), and iron-silver nanoparticles (1.6 mg/mL) and LRD (IO@AgNPs + 6 Gy). The nanoparticles and radiation doses were fractionated equally into 3 sessions during the treatment protocol

Fig. 8

Average change in the tumor size (cm.³) in control mice group (C) and mice groups treated with iron oxide nanoparticles (0.8 mg/mL) (IONPs), iron-silver nanoparticles (1.6 mg/mL) (IO@AgNPs), high radiation dose (HRD) (12 Gy), iron oxide nanoparticles (0.8 mg/mL) and low radiation dose (LRD) (6 Gy) (IONPs + 6 Gy), and iron-silver nanoparticles (1.6 mg/mL) and LRD (IO@AgNPs + 6 Gy). The nanoparticles and radiation doses were fractionated equally into 3 sessions during the treatment protocol. The data points are represented as mean ± SD (n = 5) (a, p ≤ 0.001) compared to the control group (C) and (*, p < 0.03) compared to HRD group (12 Gy)

Fig. 9

Liver histopathology photomicrographs in control mice group and mice groups treated with iron oxide nanoparticles (0.8 mg/mL) (IONPs), iron-silver nanoparticles (1.6 mg/mL) (IO@AgNPs), high radiation dose (HRD) (12 Gy), iron oxide nanoparticles (0.8 mg/mL) and low radiation dose (LRD) (6 Gy) (IONPs + 6 Gy), and iron-silver nanoparticles (1.6 mg/mL) and LRD (IO@AgNPs + 6 Gy). The nanoparticles and radiation doses were fractionated equally into 3 sessions during the treatment protocol