Efficacy of iron-silver bimetallic nanoparticles to enhance radiotherapy.

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.

Dose-dependent biological toxicity of green synthesized silver nanoparticles in rat's brain.

Metal nanoparticles, in general, and silver nanoparticles (AgNPs), in particular, have been the focus of numerous studies over the last two decades. Recently, the green synthesis of metal nanoparticles has been favored over chemical synthesis due to its low toxicity and easy preparation. The present study aims to investigate the dose-dependent toxicity of green synthesized AgNPs on rats' brains. Thirty-four Wistar male rats were divided into four groups. The first, second, and third groups were administered for 14 days with three different doses (0.5, 5, and 10 mg/kg) of AgNPs, respectively. The fourth group, which served as a control group, was given normal saline for the same period. The toxicity of the green synthesized AgNPs on the cortical and hippocampal levels of the oxidative stress markers (MDA, NO, and GSH) as well as the activity of acetylcholinesterase (AchE) and the monoamine neurotransmitters (DA, NE, and 5H-T) were investigated. AgNPs showed minimal oxidative stress in the cortex and hippocampus for the administered doses. However, AgNPs showed an inhibitory effect on AchE activity in a dose-dependent manner and a decrease in the 5H-T and NE levels. The green synthesized AgNPs showed an ultrastructural change in the cellular membranes of the neurons. The green synthesis of AgNPs has reduced their cytotoxic oxidative effects due to their capping with biologically compatible and boosting molecules such as flavonoids. However, another neurotoxicity was observed in a dose-dependent manner.

Cytotoxicity and genotoxicity of gold nanorods assisted photothermal therapy against Ehrlich carcinoma in-vivo.

AIM: Preparation of pegylated gold nanorods (PEG-AuNRs) that are capable of converting near infrared (NIR) light into heat. Evaluation of cancer therapeutic efficacy and long-term toxicity of the proposed photothermal therapy in comparison with other conventional modalities. MATERIALS AND METHODS: Prepared PEG-AuNRs were characterized by measuring their absorption spectra, zeta potential, and transmission electron microscope (TEM). Cancer therapeutic efficacy was assessed by monitoring tumor growth, measuring DNA damage and superoxide dismutase (SOD) and malondialdehyde (MDA) levels in addition to examining tumor histopathology. Further analysis concerning the toxicity of all the proposed treatment modalities was also assessed by evaluating the cytotoxicity and genotoxicity in liver and kidney tissues. KEY FINDINGS: The results demonstrated that both photothermal therapy (PEG-AuNRs + NIR laser) and chemotherapy (cisplatin) have higher efficacy in diminishing Ehrlich tumor growth with significance DNA damage over the other treatment modalities. Concerning the biosafety issue, mice treated photothermally exhibited lower MDA level and higher SOD activity in liver and kidney tissues compared with other treated groups. DNA damage represented by tail moment and olive moment of kidney tissues exhibited lower values for photothermal treated group and higher values for cisplatin treated group. SIGNIFICANCE: Photothermal therapy (PEG-AuNRs + NIR laser) potentiates higher efficacy in treating Ehrlich tumor with minimum toxicity in comparison with other conventional treatment modalities.

Magnetic fields enhance the anti-tumor efficacy of low dose cisplatin and reduce the nephrotoxicity.

The present work was to examine a combination of therapy for a low dose of cisplatin and a magnetic field (MF) on Ehrlich carcinoma-bearing mice. In this study, a total of 50 BALB/C female mice were equally distributed into five groups. Mice from the control group did not receive MF or cisplatin. The low and high dose cisplatin groups were injected intraperitoneal (i.p.) with 3 and 6 mg/kg cisplatin, respectively, on the experimental days (1, 4, and 8). Mice group of cisplatin + MF was injected with a low dose of cisplatin followed by MF exposure (50 Hz, 50 mT), and the MF group was exposed to MF only. The impact of MF and cisplatin on the tumor and kidney were evaluated by measuring superoxide dismutase (SOD) activity, malondialdehyde (MDA) and glutathione (GSH) levels, DNA injury (comet assay), histopathological investigation of tissues, and tumor progress. The results suggested that the combination of a low dose of cisplatin with MF was significantly elevated in MDA levels, reduced SOD activity, and GSH levels. Furthermore, it caused a rise in comet parameters and inhibition in tumor growth. These results showed that MF enhances the therapeutic efficacy of low cisplatin doses and reduces nephrotoxicity.

Melanin nanoparticles: Antioxidant activities and effects on γ-ray-induced DNA damage in the mouse.

The radioprotective and antioxidant activities of melanin nanoparticles (MNP) were investigated in Chinese hamster ovary (CHO) cells in vitro and BALB/C mice in vivo. The endpoints measured were cell viability, superoxide dismutase (SOD) enzyme activity, malondialdehyde (MDA) levels, DNA damage (comet assay), and histopathological examination of tissues. Irradiated groups showed decreased SOD activity and increased MDA levels. Irradiation caused a 3-10-fold increase in comet parameters such as % tail DNA. Treatment with MNP protected cells from DNA damage and death, restored SOD activity, and decreased MDA production. Synthetic MNPs have both antioxidant and radioprotective activities.

Assessment of DNA damage in Ehlrich carcinoma after treatment with doxorubicin encapsulated in nanoscales thermosensitive liposomes in combination with localized hyperthermia.

Nanoscales thermosensitive liposomes (TSL) composed of synthetic lipids (dipalmitoylphosphatidylcholine, and distearoylphosphatidylcholine), were used for doxorubicin encapsulation with 70% encapsulated efficiency. The liposomes were characterized by dynamic light scattering, transmission electron microscopy and turbidity method. Additionally, the liposomes exhibited a significant release of doxorubicin (Dox) by 60% within 5 min at 42°C. To assess the therapeutic efficacy of Dox in combination with hyperthermia, Dox free and encapsulated TSL were administered directly to Ehrlich tumor bearing mice at 1 mg/kg dose. Immediately after the drug administration, hyperthermia was applied to mention the temperature inside the tumor site at 42°C either for 5 min and 30 min. The results indicate a significant increase in the percent of apoptotic and necrotic cells in the treated group. Moreover, disrupts the integrity and the amount of intact DNA in tumor cells. In conclusion, Dox and hyperthermia may serve as a useful targeted drug delivery system for management of Ehrlich carcinoma.

Extremely low-frequency magnetic field enhances the therapeutic efficacy of low-dose cisplatin in the treatment of Ehrlich carcinoma.

The present study examines the therapeutic efficacy of the administration of low-dose cisplatin (cis) followed by exposure to extremely low-frequency magnetic field (ELF-MF), with an average intensity of 10 mT, on Ehrlich carcinoma in vivo. The cytotoxic and genotoxic actions of this combination were studied using comet assay, mitotic index (MI), and the induction of micronucleus (MN). Moreover, the inhibition of tumor growth was also measured. Treatment with cisplatin and ELF-MF (group A) increased the number of damaged cells by 54% compared with 41% for mice treated with cisplatin alone (group B), 20% for mice treated by exposure to ELF-MF (group C), and 9% for the control group (group D). Also the mitotic index decreased significantly for all treated groups (P < 0.001). The decrement percent for the treated groups (A, B, and C) were 70%, 65%, and 22%, respectively, compared with the control group (D). Additionally, the rate of tumor growth at day 12 was suppressed significantly (P < 0.001) for groups A, B, and C with respect to group (D). These results suggest that ELF-MF enhanced the cytotoxic activity of cisplatin and potentiate the benefit of using a combination of low-dose cisplatin and ELF-MF in the treatment of Ehrlich carcinoma.