Antitumor and Antibacterial Efficacy of Gallium Nanoparticles Coated by Ellagic Acid

Abstract

Cancer is a mortality contributor worldwide, and breast cancer is the most common among women. Despite the numerous breast cancer therapeutic strategies, they either have limitations or sometimes are resisted by cancer, so new approaches are needed to tackle those restrictions. Nanotechnology offers exciting leaps in the diagnosis and treatment of cancer, especially breast cancer. The main objective of this study was to investigate the effect of the newly synthesized gallium nanoparticles coated by Ellagic acid (EA-GaNPs) on the induced mammary gland carcinogenesis in female rats and their antibacterial activities comparison with standard antibiotics (Ketoconazole (100 μg/ml) and Gentamycin (4 μg/ml)) by disc diffusion method using eight different microbial species. The antitumor efficacy of EA-GaNPs was conducted both in vitro and in in vivo. The result of antimicrobial activity of EA-Ga NPs (1 mg/1 mL) revealed moderate toxicity behavior against Gram-positive {Staphylococcus aureus, Bacillus subtilis, Bacillus cereus) and Gram-negative pathogenic bacteria {Escherichia coli, Proteus vulgarfs) also, antifungal activity was detected against {Aspergillus terreus). In vitro study showed that EA-GaNPs inhibited human breast cancer cell line (MCF-7) proliferation with IC50 of 2.86 μg/ml. Although in vivo; the administration of EA-GaNPs to DMBA-treated rats ameliorated the hyperplastic state of mammary gland carcinogenesis induced by DMBA. Additionally, EA-GaNPs administration significantly modulated the activities of ALT and AST, as well as the levels of urea and creatinine in serum. Also, EA-GaNPs administration improved the antioxidant state by increasing Superoxide dismutase activity and GSH content, and decreasing malondialdehyde content in the mammary tissue, besides enhancing the apoptotic activity through elevating the levels of caspase-3 and decreasing the protein intensities of protein kinase B & phosphatidyl inositide 3-kinases. Furthermore, a significant decrease in serum Total iron-binding capacity accompanied by a significant increase in the level of calcium was noted. So, it can be concluded that the newly synthesized nanoparticles EA-GaNPs have an efficient antitumor activity that was manifested by reduction of the viability on the human breast cancer cell line (MCF-7) in vitro. Also, in vivo against the chemically induced mammary gland carcinogenesis in a female rat model. Histopathological findings were in harmony with biochemical and molecular results showing the effectiveness of EA-GaNPs against mammary carcinogenesis. Therefore, EA-GaNPs could be a promising, potent anti-cancer compound.

Development of Gallium(III) as an Antimicrobial Drug Targeting Pathophysiologic Iron Metabolism of Human Pathogens

“…El-Sonbaty investigated the use of gallium nanoparticles coated in ellagic acid against the Gram-positive pathogens S. aureus , B. subtilis , and Bacillus cereus in a disc diffusion assay. They observed modest levels of inhibition with zones of inhibition ranging from 10 to 14 mm, all of which were smaller than their reference drugs …”

“…They observed modest levels of inhibition with zones of inhibition ranging from 10 to 14 mm, all of which were smaller than their reference drugs. 174 Best et al used three different polysaccharides, carboxymethyl cellulose (CMC), alginate, and pectin, as delivery vehicles for gallium. They were then tested against P. aeruginosa, E. coli, and S. aureus by finding their MICs, and minimum bactericidal concentrations (MBCs).…”

Bioinorganic Modulators of Ferroptosis: A Review of Recent Findings

“…It was also confirmed as hepatoprotective and renoprotective in the course of in vivo testing against 7, 12 dimethylbenz[a] anthracene (DMBA)-induced mammary gland carcinogenesis in rats. Yet again, the authors did not specifically investigate the possible ferroptotic character of the reported cellular response, focusing on how efficient the antitumor activity was, but a few relevant observations can be made [ 75 ]. The nanoparticles decreased the level of alanine transaminase and aspartate aminotransferase.…”

“…Less malondialdehyde, on the other hand, was indicative of an inhibited lipid peroxidation process in cancer cells [ 78 ]. The gallium atoms likely contributed to normalizing the serum level of iron, as reflected by lower total iron-binding capacity (TIBC) relative to the DMBA iron-deficient group, where much of iron supply was consumed by malignant cells [ 75 ]. How much of the reported antitumor effect was related to the ferroptosis-inducing properties of the gallium-based agent remains up for debate.…”

Chitosan-Coated Niosomes Loaded with Ellagic Acid Present Antiaging Activity in a Skin Cell Line

“…Pomegranate fruit extract (PFE) shows antioxidative activity caused by the action of EA . Research findings show that EA is a potential biomolecule with remarkable biological features, such as UV shielding and anticancer functionalities. − It is also a potent antioxidant and antibacterial agent. , EA is made up of four hydroxyl groups and several lactone rings, which are hydrophilic . However, its low bioavailability limits its therapeutic effect .…”