Combination of graphene oxide–silver nanoparticle nanocomposites and cisplatin enhances apoptosis and autophagy in human cervical cancer cells

Abstract

Background Cisplatin (Cis) is a widely used chemotherapeutic drug for treating a variety of cancers, due to its ability to induce cell death in cancer cells significantly. Recently, graphene and its modified nanocomposites have gained much interest in cancer therapy, due to their unique physicochemical properties. The objective of this study was to investigate the combination effect of Cis and a reduced graphene oxide–silver nanoparticle nanocomposite (rGO-AgNPs) in human cervical cancer (HeLa) cells. Materials and methods We synthesized AgNPs, rGO, and rGO-AgNP nanocomposites using C-phycocyanin. The synthesized nanomaterials were characterized using various analytical techniques. The anticancer properties of the Cis, rGO-AgNPs, and combination of Cis and rGO-AgNPs were evaluated using a series of cellular assays, such as cell viability, cell proliferation, LDH leakage, reactive oxygen species generation, and cellular levels of oxidative and antioxidative stress markers such as malondialdehyde, glutathione, SOD, and CAT. The expression of proapoptotic, antiapoptotic, and autophagy genes were measured using real-time reverse-transcription polymerase chain reaction. Results The synthesized AgNPs were well dispersed, homogeneous, and spherical, with an average size of 10 nm and uniformly distributed on graphene sheets. Cis, GO, rGO, AgNPs, and rGO-AgNPs inhibited cell viability in a dose-dependent manner. The combination of Cis and rGO-AgNPs showed significant effects on cell proliferation, cytotoxicity, and apoptosis. The combination of Cis and rGO-AgNPs had more pronounced effects on the expression of apoptotic and autophagy genes, and also significantly induced the accumulation of autophagosomes and autophagolysosomes, which was associated with the generation of reactive oxygen species. Conclusion Our findings substantiated rGO-AgNPs strongly potentiating Cis-induced cytotoxicity, apoptosis, and autophagy in HeLa cells, and hence rGO-AgNPs could be potentially applied to cervical cancer treatment as a powerful synergistic agent with Cis or any other chemotherapeutic agents.

Redox‐Responsive Nanocomposites Composed of Graphene Oxide and Chlorin e6 for Photodynamic Treatment of Cholangiocarcinoma

“…Many researchers investigated GO as a platform for nanomaterials such as gold nanoparticles, magnetic nanoparticles, silver nanoparticles, quantum‐dot, and etc . Yuan and Gurunathan synthesized nanocomposites composed of GO‐silver nanoparticles and nanocomposites have synergistic anticancer activity with cisplatin . Those nanocomposites induced apoptosis of cancer cells and accumulated autophagosomes/autophagolysosomes related to ROS generation.…”

“…administration because GO drug carriers have low hemolysis activity. Many researchers investigated GO as a platform for nanomaterials such as gold nanoparticles, magnetic nanoparticles, silver nanoparticles, quantum‐dot, and etc . Yuan and Gurunathan synthesized nanocomposites composed of GO‐silver nanoparticles and nanocomposites have synergistic anticancer activity with cisplatin .…”

siRNA-loaded selenium nanoparticle modified with hyaluronic acid for enhanced hepatocellular carcinoma therapy

“…33 As shown in Figure 6B, the treatment with HA-Se-PEI@siRNA markedly induced HepG2 cell apoptosis and obtained higher apoptosis rate (~32.7%) compared with Se-PEI@siRNA (~27.7%) and Lipofectamine 2000@siRNA (~17.9%). However, no obvious cell apoptosis was observed in the HA-Se-PEI@ siNC-treatment group, suggesting that the silence of HES5 contributed to the apoptosis of HepG2 cells.…”

The Current Understanding of Autophagy in Nanomaterial Toxicity and Its Implementation in Safety Assessment-Related Alternative Testing Strategies

“…Silver has been used in our lives throughout history and recently for many medical applications due to its effectiveness in arresting the growth of microorganisms [115]. Recent studies have shown the enormous therapeutic potential of AgNPs against numerous cancer cells by modulating autophagy action as cytotoxic agents or as nanocarriers that, combined with other treatments, deliver therapeutic molecules [116,117]. The toxicity of AgNPs has been suggested as the result of lysosome-dependent silver ion release that leads to massive ROS production.…”