Modulation of Cancer Cell Autophagic Responses by Graphene-Based Nanomaterials: Molecular Mechanisms and Therapeutic Implications

Abstract

Graphene-based nanomaterials (GNM) are plausible candidates for cancer therapeutics and drug delivery systems. Pure graphene and graphene oxide nanoparticles, as well as graphene quantum dots and graphene nanofibers, were all able to trigger autophagy in cancer cells through both transcriptional and post-transcriptional mechanisms involving oxidative/endoplasmic reticulum stress, AMP-activated protein kinase, mechanistic target of rapamycin, mitogen-activated protein kinase, and Toll-like receptor signaling. This was often coupled with lysosomal dysfunction and subsequent blockade of autophagic flux, which additionally increased the accumulation of autophagy mediators that participated in apoptotic, necrotic, or necroptotic death of cancer cells and influenced the immune response against the tumor. In this review, we analyze molecular mechanisms and structure–activity relationships of GNM-mediated autophagy modulation, its consequences for cancer cell survival/death and anti-tumor immune response, and the possible implications for the use of GNM in cancer therapy.

The Preliminary Study on the Proapoptotic Effect of Reduced Graphene Oxide in Breast Cancer Cell Lines

“…rGO is widely used as a drug or gene delivery system and its use in breast cancer therapy has been suggested [20]. Several studies have shown cytotoxic effects of GO on normal, cancerous and bacterial cells, although toxicological information on rGO materials remains limited [11,13,21]. In our study, we examined the cytotoxic effects of rGO nanomaterials on breast cancer cell lines.…”

“…To date, there are no clear mechanisms by which rGO induces cytotoxicity. Various physiochemical properties of rGO, including size, shape, structure, hydrophobicity, surface functionalization, dose administration, purity and elemental composition, allow rGO to exhibit many mechanisms of action in cancer cells [9][10][11]. Key mechanisms that appear to be related to GFNs include the production of reactive oxygen species (ROS).…”

“…Key mechanisms that appear to be related to GFNs include the production of reactive oxygen species (ROS). The oxidative stress observed after the administration of rGO is usually caused by a decrease in the main antioxidant glutathione (the GSH-reduced form) and a strong increase in the ROS level [11].…”

The Reduced Graphene Oxide (rGO) Induces Apoptosis, Autophagy and Cell Cycle Arrest in Breast Cancer Cells

“…Graphene is isolated from crystalline graphite Graphene is a flat monolayer composed of a single atom thick, two-dimensional sheet of a hexagonally arranged honeycomb lattice [ 6 ]. Graphene-based nanomaterials (GNM) include nanodimensional flakes or ribbons of pure graphene, graphene oxide (GO) and reduced graphene oxide (rGO) all consisting of single graphene layers [ 7 , 8 ]. GNM have various applications and are generally used in the biomedical field in diagnostics, bio-imaging and drug delivery systems.…”

Characteristics of Graphene Oxide for Gene Transfection and Controlled Release in Breast Cancer Cells

“…This process can lead to the breakage, modification, or further cross-linking of the molecular chains. Cellular proteins and DNA can, therefore, undergo modification or even a complete loss of their biological activities [ 144 ].…”