Peanut-Shaped Gold Nanoparticles with Shells of Ceragenin CSA-131 Display the Ability to Inhibit Ovarian Cancer Growth In Vitro and in a Tumor Xenograft Model

Abstract

Gold nanoparticles-assisted delivery of antineoplastics into cancerous cells is presented as an effective approach for overcoming the limitations of systemic chemotherapy. Although ceragenins show great potential as anti-cancer agents, in some tumors, effective inhibition of cancer cells proliferation requires application of ceragenins at doses within their hemolytic range. For the purpose of toxicity/efficiency ratio control, peanut-shaped gold nanoparticles (AuP NPs) were functionalized with a shell of ceragenin CSA-131 and the cytotoxicity of AuP@CSA-131 against ovarian cancer SKOV-3 cells and were then analyzed. In vivo efficiency of intravenously and intratumorally administered CSA-131 and AuP@CSA-131 was examined using a xenograft ovarian cancer model. Serum parameters were estimated using ELISA methods. Comparative analysis revealed that AuP@CSA-131 exerted stronger anti-cancer effects than free ceragenin, which was determined by enhanced ability to induce caspase-dependent apoptosis and autophagy processes via reactive oxygen species (ROS)-mediated pathways. In an animal study, AuP@CSA-131 was characterized by delayed clearance and prolonged blood circulation when compared with free ceragenin, as well as enhanced anti-tumor efficiency, particularly when applied intratumorally. Administration of CSA-131 and AuP@CSA-131 prevented the inflammatory response associated with cancer development. These results present the possibility of employing non-spherical gold nanoparticles as an effective nanoplatform for the delivery of antineoplastics for the treatment of ovarian malignancy.

Green Synthesis of Gold Nanoflowers Using Rosmarinus officinalis and Helichrysum italicum Extracts: Comparative Studies of Their Antimicrobial and Antibiofilm Activities

“…STEM image results demonstrated that H-AuNFs have a different morphology consisting of poly-dispersed, triangle, pentagon, and nearly spherical shapes, while R-AuNFs are nearly spherical. In the literature [ 72 , 73 , 74 , 75 ] spherical, triangular, and hexagonal gold nanoparticles have been reported; however, in this study, flower-shaped nanoparticles were also obtained in agreement with Borah et al [ 24 ].…”

Ceragenin CSA-13 displays high antibacterial efficiency in a mouse model of urinary tract infection

“…Moreover, we would like to note that histopathological analysis of bladder samples collected from treated animals confirmed that the markers of inflammation (tissue edema, exfoliation of transitional epithelial cells, invasion of inflammatory cells in the mucosa, fibrosis of the lamina propria, and bladder mucosa hyperplasia) were considerably decreased in ceragenin-treated animals when compared to control ones. Moreover, the ability of ceragenin to diminish inflammation induced by pathological process was also presented by our research team when analyzing the anti-cancer activities of CSA-131 and its nanosystem 61 . A compelling body of evidence confirms also that the elastic modulus is an important factor influencing bacterial attachment, growth and biofilm formation, suggesting that the stiffening of tissues upon ceragenin administration in UTI-suffering animals creates an environment unfavorable for bacteria replication and virulency.…”

Metallic Nanosystems in the Development of Antimicrobial Strategies with High Antimicrobial Activity and High Biocompatibility

“…Therefore, different methods are used to assess the biocompatibility of nanoparticles, ranging from quantitative assays using conversion of compounds such as 3-(4, 5dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) [257], 2, 3-bis-(2-methoxy-4nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) [258] or lactate dehydrogenase (LDH) [257], through qualitative studies (live and/or dead cell staining assays using dyes such as calcein-AM with propidium iodide [259] and dual acridine orange/ethidium bromide staining [260]) and finally blood hemolysis assays [261] and animal model [262] to assess biocompatibility.…”