Anti-Angiogenic and Anti-Proliferative Graphene Oxide Nanosheets for Tumor Cell Therapy

Abstract

Graphene oxide (GO) is a bidimensional novel material that exhibits high biocompatibility and angiogenic properties, mostly related to the intracellular formation of reactive oxygen species (ROS). In this work, we set up an experimental methodology for the fabrication of GO@peptide hybrids by the immobilization, via irreversible physical adsorption, of the Ac-(GHHPH)4-NH2 peptide sequence, known to mimic the anti-angiogenic domain of the histidine-proline-rich glycoprotein (HPRG). The anti-proliferative capability of the graphene-peptide hybrids were tested in vitro by viability assays on prostate cancer cells (PC-3 line), human neuroblastoma (SH-SY5Y), and human retinal endothelial cells (primary HREC). The anti-angiogenic response of the two cellular models of angiogenesis, namely endothelial and prostate cancer cells, was scrutinized by prostaglandin E2 (PGE2) release and wound scratch assays, to correlate the activation of inflammatory response upon the cell treatments with the GO@peptide nanocomposites to the cell migration processes. Results showed that the GO@peptide nanoassemblies not only effectively induced toxicity in the prostate cancer cells, but also strongly blocked the cell migration and inhibited the prostaglandin-mediated inflammatory process both in PC-3 and in HRECs. Moreover, the cytotoxic mechanism and the internalization efficiency of the theranostic nanoplatforms, investigated by mitochondrial ROS production analyses and confocal microscopy imaging, unraveled a dose-dependent manifold mechanism of action performed by the hybrid nanoassemblies against the PC-3 cells, with the detection of the GO-characteristic cell wrapping and mitochondrial perturbation. The obtained results pointed out to the very promising potential of the synthetized graphene-based hybrids for cancer therapy.

Nanomaterials for cancer therapy: current progress and perspectives

“…Graphene-based nanomaterials can be classified into several types depending on their composition, structure, and properties: single-layer graphene, multi-layer graphene, graphene oxide (GO) and reduced graphene oxide (rGO) [ 122 ]. Graphene has unique electrochemical and mechanical properties, for example, optical transmittance, chemical inertness, high density, molecular barrier abilities and high hydrophobicity [ 123 , 124 ]. Graphene also has other remarkable features that contribute to cancer theragnostic such as high planar surface enabling higher drug-loading capacity [ 125 ] and thermal conductivity (5000 W/mK) [ 126 ].…”

Current Progress in Cancer Treatment Using Nanomaterials

“…Graphene shows unique mechanical and electrochemical advantages. Optical transmittance, high density, and hydrophobicity are outstanding properties ( 89 , 90 ). In addition, high drug-carrying ability and thermal conductivity are important properties in cancer theragnostic ( 91 , 92 ).…”

Advances in Drug Delivery Nanosystems Using Graphene-Based Materials and Carbon Nanotubes

“…GO@peptide hybrids fabricated through irreversible physical adsorption of the Ac-(GHHPH) 4 -NH 2 peptide sequence, known to mimic the anti-angiogenic domain of the histidine-proline-rich glycoprotein, showed powerful toxicity to PC-3 prostate cells, effectively inhibited the cell migration, and inhibited the prostaglandin-mediated inflammatory process not only in PC-3 cells but also in human retinal endothelial cells. The mechanism of action of GO@peptide hybrids against the PC-3 cells consisted of GO-characteristic cell wrapping and mitochondrial perturbation [ 211 ]. Scaffolds fabricated using silk fibroin combined with functionalized GO loaded with a high amount of salvianolic acid B ( Figure 7 ) continuously released the drug at maintaining its biological activity, pronouncedly stimulated the osteogenic differentiation of rat bone marrow mesenchymal stem cells, and strongly enhanced endothelial cell (EA-hy9.26) migration and tubulogenesis in vitro.…”