ROS-Mediated Apoptosis and Autophagy in Ovarian Cancer Cells Treated with Peanut-Shaped Gold Nanoparticles

Abstract

Background Even with considerable improvement in treatment of epithelial ovarian cancer achieved in recent years, an increasing chemotherapy resistance and disease 5-year relapse is recorded for a majority part of patients that encourages the search for better therapeutic options. Gold nanoparticles (Au NPs) due to plethora of unique physiochemical features are thoroughly tested as drug delivery, radiosensitizers, as well as photothermal and photodynamic therapy agents. Importantly, due to highly controlled synthesis, it is possible to obtain nanomaterials with directed size and shape. Methods In this work, we developed novel elongated-type gold nanoparticles in the shape of nanopeanuts (AuP NPs) and investigated their cytotoxic potential against ovarian cancer cells SKOV-3 using colorimetric and fluorimetric methods, Western blot, flow cytometry, and fluorescence microscopy. Results Peanut-shaped gold nanoparticles showed high anti-cancer activity in vitro against SKOV-3 cells at doses of 1–5 ng/mL upon 72 hours treatment. We demonstrate that AuP NPs decrease the viability and proliferation capability of ovarian cancer cells by triggering cell apoptosis and autophagy, as evidenced by flow cytometry and Western blot analyses. The overproduction of reactive oxygen species (ROS) was noted to be a critical mediator of AuP NPs-mediated cell death. Conclusion These data indicate that gold nanopeanuts might be developed as nanotherapeutics against ovarian cancer.

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

“…In the majority of reported studies, gold nanorods were also characterized by higher cellular uptake efficiency, thus presenting an improved drug delivery efficiency when compared with spherical ones [50,51]. Indeed, our previous research revealed that peanut-shaped gold nanoparticles are far more effective against cancer cells than those spherical ones ( [22]; see Supplementary Materials). Moreover, a nanosystem consisting of CSA-131 attached to the surface of spherical-shaped gold NPs was not efficient enough against ovarian cancer cells.…”

“…Immunostaining of cells exposed to CSA-131 and AuP@CSA-131 for 72 h was performed in order to visualize alterations in the expression of proteins related to cell killing processes. For this purpose, treated SKOV-3 cells were fixed, permeabilized, blocked with 0.1% bovine serum albumin (BSA) and incubated with antibodies against apoptotic (NOX4, annexin A1, cleaved caspase-3, cleaved caspase-9) and autophagic proteins (Atg12 and Beclin-1) according to the previously presented protocol [22].…”

“…To quantitively estimate the alterations in ceragenin-affected signaling pathways, SKOV-3 cells were cultured for 72 h with increasing concentrations of CSA-131 and AuP@CSA-131, followed by Western blot analysis, according to the protocol in our previous paper [22].…”

“…Alterations in the functioning of ovarian cancer cells mitochondria upon exposure to CSA-131 and AuP@CSA-131 at doses of 2, 5 and 10 µg/mL were measured using the NucleoCounter ® NC-3000™ fluorescence image cytometer, according to the protocol presented in our previous paper [22].…”

“…As a continuation of our previous in vitro study demonstrating the potent anti-cancer activity of peanut-shaped gold nanoparticles (AuP NPs) when compared with spherical-shaped nanomaterials ( [22]; see Supplementary Materials), we examined the usefulness of these elongated-type nanostructures as carriers for the delivery of ceragenin CSA-131 into ovarian cancer cells. Ceragenins, due to their favorable pharmacokinetic and pharmacodynamic features, such as non-specific potent membrane activity, stability in physiological fluids and reduced susceptibility to development of drug resistance, have been successfully tested as potent antimicrobials with clinical applicability for the treatment of drug-resistant bacteria and fungal infections [23][24][25][26].…”