Recent advances in γH2AX biomarker-based genotoxicity assays: A marker of DNA damage and repair.

The phosphorylation of histone variant H2AX and formation of γH2AX is a primary response to the DNA double-strand breaks (DSBs). Detection of γH2AX is a robust and sensitive tool for diagnosis of DNA damage and repair in pre-clinical drug discovery investigations. In addition, the replication stress also leads to the formation of γH2AX and cell death and so γH2AX can serve as a surrogate marker of drug-induced cytotoxicity. Recent advances in genomic research offer an opportunity to detect γH2AX as a specific biomarker for quantitative analysis of DNA damages and repair using high content screening technology and quantitative imaging analysis. The proposed approaches identify a wide range of genetic disorders and are applied in combination with other assays in drug discovery and also for the evaluation of the efficacy of various developmental drugs. In the current review, we provide recent insights into the potential of γH2AX biomarker as a powerful tool in genotoxicity analyses for the monitoring and managing of cancer diseases.

Doxorubicin and doxorubicin-loaded nanoliposome induce senescence by enhancing oxidative stress, hepatotoxicity, and in vivo genotoxicity in male Wistar rats.

The senescence phenomenon is historically considered as a tumor-suppressing mechanism that can permanently arrest the proliferation of damaged cells, and prevent tumor eradication by activating cell cycle regulatory pathways. Doxorubicin (DX) as an antineoplastic agent has been used for the treatment of solid and hematological malignancies for a long time, but its clinical use is limited due to irreversible toxicity on off-target tissues. Thereby, the encapsulation of plain drugs in a vehicle may decrease the side effects while increasing their permeability and availability in target cells. Here, we aimed to investigate and compare the effects of DX and DX-loaded nanoliposome (NLDX) on the induction of senescence via assessment of the occurrence of apoptosis/necrosis, genomic damage, oxidative stress, and liver pathologies. The study groups included DX (0.75, 0.5, 0.1 mg/kg/BW), NLDX groups (0.1, 0.05, 0.025 mg/kg/BW), and an untreated control group. The liver tissues were used to investigate the oxidative stress parameters and probable biochemical and histopathological alterations. Annexin V/PI staining was carried out to find the type of cellular death in the liver tissue of healthy rats exposed to different concentrations of DOX and LDOX. Data revealed that the highest dose of NLDX (0.1 mg/kg/BW) could significantly induce cellular senescence throughout significant increasing the level of genotoxic damage (p < 0.0001) and the oxidative stress (p < 0.001) compared with a similar dose of DX, in which the obtained results were further confirmed by flow cytometry and histopathological assessments of the liver tissue. This investigation provides sufficient evidence of improved therapeutic efficacy of NLDX compared with plain DX in male Wistar rats.

Recent trends in targeted therapy of cancer using graphene oxide-modified multifunctional nanomedicines.

Rapid progresses in nanotechnology fields have led us to use a number of advanced nanomaterials (NMs) for engineering smart multifunctional nanoparticles (NPs)/nanosystems (NSs) for targeted diagnosis and therapy of various diseases including different types of malignancies. For the effective therapy of any type of solid tumor, the treatment modality should ideally solely target the aberrant cancerous cells/tissue with no/trivial impacts on the healthy cells. One approach to achieve such unprecedented impacts can be fulfilled through the use of seamless multimodal NPs/NSs with photoacoustic properties that can be achieved using advanced NMs such as graphene oxide (GO). It is considered as one of the most promising materials that have been used in the development of various NPs/NSs. GO-based targeted NSs can be engineered as programmable drug delivery systems (DDSs) to perform on-demand chemotherapy combined with photonic energy for photothermal therapy (PTT) or photodynamic therapy (PDT). In the current review, we provide important insights on the GO-based NSs and discuss their potentials for the photodynamic/photothermal ablation of cancer in combination with anticancer agents.

Nano graphene oxide: a novel carrier for oral delivery of flavonoids.

The interesting physical and chemical properties of graphene oxide (GO) have led to much excitement among biomedical scientists in recent years. It is known that many potent, often aromatic medicines are water insoluble, and this has hindered their administration to treat diseases. Nano GO was synthesized and investigated for its biological application as a carrier for quercetin, a focused bioactive flavonoid widely used as a health supplement and a drug candidate. Different techniques were used to fully evaluate the synthesis, cytotoxicity, and quercetin loading capacity of nano GO. AFM and TEM results confirmed the preparation of planar nanoparticles without aggregation which was verified by reported size results (30 nm) obtained with a particle size analyzer. FTIR and DSC results proved the drug-carrier interaction. In vitro cytotoxicity assays showed that nano GO had no cytotoxicity on A549 cells in different amounts after incubation for 72 h, confirming its suitability as a drug carrier. Our results showed that nano GO can be proposed as a new carrier due to its small size, large specific surface area, low cost, and useful non-covalent interactions with aromatic low-soluble flavonoids such as quercetin. Moreover, it may find widespread applications in biomedicine.