Accordingly, different signaling pathways resulting in the proliferative or anti-proliferative effects could be activated. The effects induced by the GO@T hybrids and GO+T mixtures on PC-3 and HREC cell viability confirm that, depending on the incubation time and the dose of treatment, it could be also used as an anti-cancer molecule and not only as a drug-delivery agent [63]. 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 Pindolol wrapping and mitochondrial perturbation. The obtained results pointed out to the very promising potential of the synthetized graphene-based hybrids for malignancy therapy. and studies [21]. Thus, Liu et al. formulated transferrin altered graphene oxide for glioma-targeted drug delivery [22], Li et al. used functionalized nano-graphene oxide particles for targeted fluorescence imaging and photothermic therapy of glioma U251 cells [23], while Track and colleagues evaluated hyaluronic acid-decorated graphene oxide nanohybrids as service providers for targeted and pH-responsive anticancer therapy [24]. Furthermore, GO shows intrinsic biological properties, including antimicrobial activity [25] and the capability to control the function of immune cells [26] and to modulate angiogenesis. This latter feature provides additional advantages in malignancy therapy, since formation of new blood vessels is usually involved in both tumor growth and development of metastases [21,27]. Hence, the anti-angiogenic action of GO can be very effective to fight cancer. To note, there are plenty of examples in the literature on the development of GO and modified GO platforms for anti-cancer therapy [28,29,30,31]. It has been exhibited that GO linens present pro-angiogenic properties at low doses (1C50 ng/mL), due to the controlled production of intracellular Pindolol reactive oxygen species (ROS) (H2O2 and O2??) induced by this material, while show Pindolol anti-angiogenic features at high doses (100 ng/mL), attributed to the excessive generation of intracellular ROS [32]. In general, the mechanisms underlying GO toxicity in addition to oxidative stress and excessive ROS production also include DNA damage, apoptosis, autophagy, and immune responses, which widely varied in relation to the physical-chemical properties of GO, such as surface chemistry, layer number, lateral dimensions, and purity [33]. The histidine-proline-rich glycoprotein (HPRG) is usually a single polypeptide chain protein of 70C75 kDa, with a multidomain structure. In humans, Pindolol the protein is usually synthesized in the liver and is present in plasma at relatively high concentrations of 100C150 g/mL (1.5 M) [34,35]. HPRG ability to simultaneously interact with several ligands suggests that it may act as an adapter molecule which regulates numerous biological processes, including blood coagulation and fibrinolysis, adhesion, and cell migration, as well as anti-/pro-angiogenic activity [36]. Indeed, the HPRG protein promotes angiogenesis by inhibiting the activity of the antiangiogenic thrombospondin-1 (TPS-1) [37], by binding to plasminogen/plasmin onto the surface of endothelial cells as well as by promoting cell migration and invasion [38], which are crucial phases of the new blood vessels formation. On the other hand, HPRG has also a exhibited antiangiogenic activity, mainly localized in its histidine-proline-rich domain name (H/P) and occurring by the blocking of the conversation between fibroblast growth factor (FGF-1 and FGF-2) and heparan sulphate in the extracellular matrix (ECM) and the surface of endothelial cells [39]. The AcC(GHHPH)4CNH2 peptide has been shown to be an active HPRG mimic system, and it has been exhibited effective as antitumor agent in two syngeneic malignancy models, namely Lewis lung malignancy (3LL) and melanoma (B16F1) growth in mice [40,41]. Based on these premises, in this work GO was functionalized with a with the AcC(GHHPH)4GKCNH2 peptide [41] covalently bound to a 5,6-carboxyfluorescein (Fam) moiety, hereinafter named Tetra(HPRG)-Fam. The integration of the therapeutic potential from both GO and the Tetra(HPRG) peptide and the imaging capability through the fluorescence of the dye-labelled peptide Rabbit polyclonal to EPHA4 makes the hybrid graphene oxide-Tetra(HPRG)Fam system (hereinafter named GO@T) a potential theranostic Pindolol platform. The physicochemical characterization was carried out by mean of spectroscopic analyses of UV-visible, fluorescence and ATR-FTIR, to scrutinize the hybrid biointerface between the nanosheets and the peptide molecules in terms of electron.