Cationic graphene oxide nanoplatform mediates miR-101 delivery to promote apoptosis by regulating autophagy and stress

Abstract

IntroductionMicroRNA-101 (miR-101) is an intense cancer suppressor with special algorithm to target a wide range of pathways and genes which indicates the ability to regulate apoptosis, cellular stress, metastasis, autophagy, and tumor growth. Silencing of some genes such as Stathmin1 with miR-101 can be interpreted as apoptotic accelerator and autophagy suppressor. It is hypothesized that hybrid microRNA (miRNA) delivery structures based on cationized graphene oxide (GO) could take superiority of targeting and photothermal therapy to suppress the cancer cells.Materials and methodsIn this study, GO nanoplatforms were covalently decorated with polyethylene glycol (PEG) and poly-l-arginine (P-l-Arg) that reduced the surface of GO and increased the near infrared absorption ~7.5-fold higher than nonreduced GO.ResultsThe prepared nanoplatform [GO-PEG-(P-l-Arg)] showed higher miRNA payload and greater internalization and facilitated endosomal scape into the cytoplasm in comparison with GO-PEG. Furthermore, applying P-l-Arg, as a targeting agent, greatly improved the selective transfection of nanoplatform in cancer cells (MCF7, MDA-MB-231) in comparison with immortalized breast cells and fibroblast primary cells. Treating cancer cells with GO-PEG-(P-l-Arg)/miR-101 and incorporating near infrared laser irradiation induced 68% apoptosis and suppressed Stathmin1 protein.ConclusionThe obtained results indicated that GO-PEG-(P-l-Arg) would be a suitable targeted delivery system of miR-101 transfection that could downregulate autophagy and conduct thermal stress to activate apoptotic cascades when combined with photothermal therapy.

Graphenic Materials for Biomedical Applications

“…It is known that GOs with lateral dimensions higher than 100 nm do not easily penetrate into cells, however GO flakes of approximately 100 nm and less can readily cross the cell membrane. If the diameter reaches below 40 nm, their penetration in the cells may be further increased [27].…”

“…Characteristic absorbance at 300 nm is done by π→π* transitions of C=C bond and the n→π* transitions of C=O bond, respectively. Upon the binding of the functional groups to C=C bonds, a shift from 230 to 266 nm occurs, and the shoulder at 300 nm is reduced [27,40,45]. The proper characterization of materials used to explore possibilities outside of biomedical technologies is one of the most important steps.…”

“…The unstable structure, negative charge, and poor cellular uptake of genes make the usage of a carrier necessary for their protection and transport. GR NPs covered by guanidine and amine moieties possess better potential for coupling with genes (i.e., in DNA or RNA) [27].…”

“…In addition to detection, GO can protect gene therapeutics from nuclease degradation and streamline treatment by increasing intracellular drug delivery that can be covalently or non-covalently associated with various functionalization approaches [140]. For example, hybrid miRNA provides GO with positive functional groups that could take superiority over targeting and PTT when suppressing cancer cells [27]. MicroRNA-101 (miR-101) is a significant regulatory factor that is downregulated in various cancer types, such as prostate, liver, lung, breast, pancreatic cancer, bladder, and colon cancer.…”

“…In addition, the application of P-l-Arg has been shown to increase the selective transfection of systems in tumors (MCF7, MDA-MB-231) as compared to immortalized breast and fibroblast cells. The application of GO-PEG-(P-l-Arg)/miR-101 and NIR irradiation has been shown to induce a 68% occurrence of apoptosis in cancer cells and suppress the Stathmin1 protein [27,65].…”