A Graphene Oxide-Angiogenin Theranostic Nanoplatform for the Therapeutic Targeting of Angiogenic Processes: The Effect of Copper-Supplemented Medium

Abstract

Graphene oxide (GO) nanosheets with different content in the defective carbon species bound to oxygen sp3 were functionalized with the angiogenin (ANG) protein, to create a novel nanomedicine for modulating angiogenic processes in cancer therapies. The GO@ANG nanocomposite was scrutinized utilizing UV-visible and fluorescence spectroscopies. GO exhibits pro- or antiangiogenic effects, mostly attributed to the disturbance of ROS concentration, depending both on the total concentration (i.e., >100 ng/mL) as well as on the number of carbon species oxidized, that is, the C/O ratio. ANG is considered one of the most effective angiogenic factors that plays a vital role in the angiogenic process, often in a synergic role with copper ions. Based on these starting hypotheses, the GO@ANG nanotoxicity was assessed with the MTT colorimetric assay, both in the absence and in the presence of copper ions, by in vitro cellular experiments on human prostatic cancer cells (PC-3 line). Laser confocal microscopy (LSM) cell imaging evidenced an enhanced internationalization of GO@ANG than bare GO nanosheets, as well as significant changes in cell cytoskeleton organization and mitochondrial staining compared to the cell treatments with free ANG.

Reduced graphene oxide coated alginate scaffolds: potential for cardiac patch application

“…In vivo assessment of subcutaneously implanted rGO-COL scaffolds after 1 and 3 weeks post-implantation in mice further approved improved cell infiltration within the electroactive scaffolds as well as the angiogenic properties of rGO-incorporated constructs due to the presence of rGO [ 12 ]. Altogether, the increase in gene and protein expression of VEGFR2 on the rGO-coated scaffolds could be due to the angiogenic-inducing properties of rGO, which have been similarly shown in previous studies [ 81 , 82 ].…”

The Hybrid Nano-Biointerface between Proteins/Peptides and Two-Dimensional Nanomaterials

“…The adsorption of proteins on GO can also modify the nanosheets' toxicity. GO functionalized with the angiogenin (ANG) protein represents a novel nanomedicine for modulating angiogenesis [51,52]. ANG is a powerful angiogenic factor [53,54] and a target for nanomaterial-based anticancer therapies [55,56].…”

Cisplatin binding to angiogenin protein: new molecular pathways and targets for the drug's anticancer activity

“…29 In previous works, we exploited, by in vitro tests in the PC-3 prostate cancer cell line, the capability to promote ROS formation by nanomaterials functionalized with peptides with angiogenic properties or just CisPt as well as the inhibition of cell migration. [30][31][32] In the present work, we investigate the interaction between CisPt and Ang (i.e., we study the formation of the Ang@CisPt adduct) using X-ray crystallography, UV-visible (UV-vis) and circular dichroism (CD) spectroscopies, and high-resolution electrospray ionization (ESI) mass spectrometry. As per the cellular experiments, in this work we focused on the cytotoxicity and related perturbation/damage mechanisms in cancer cells.…”

“…29 In previous works, we exploited, by in vitro tests in the PC-3 prostate cancer cell line, the capability to promote ROS formation by nanomaterials functionalized with peptides with angiogenic properties or just CisPt as well as the inhibition of cell migration. 30–32…”