Monkeypox and drug repurposing: seven potential antivirals to combat the viral disease.

The growing concern about the monkeypox (Mpox) virus infection has garnered a lot of public attention. However, the treatment options available to combat the same is limited to tecovirimat. Additionally, in a possible incidence of resistance, hypersensitivity, or adverse drug reaction, it is imperative to devise and reinforce the second-line therapy. Thus, in this editorial, the authors suggest seven antiviral drugs that could potentially be repurposed to combat the viral illness.

Fabrication of methotrexate-loaded gold nanoconjugates and its enhanced anticancer activity in breast cancer.

Methotrexate (MTX) is known antagonist of folic acid and widely used as an anti-cancer drug. The folate receptor (FR) and reduced folate carrier are mostly responsible for internalization of methotrexate in tumor cells. Mutation in reduced folate carrier (RFC) leads to resistance against MTX in various tumor cell lines including MDA-MB-231 breast cancer cells. To overcome the resistance of MTX, folate receptor targeted nanoparticles have been commonly used for targeting breast tumors. The aim of the study is to determine the ability of methotrexate gold nanoparticles (MTX-GNPs) in the induction of apoptosis and to explore the molecular changes at genomics and proteomics level. Different assays like cell viability assay, cell cycle analysis, apoptosis, real-time PCR and western blot were carried out to evaluate the anti-cancer effect of MTX-Gold NPs on MCF-7 and MDA-MB-231 cells. Our observations demonstrated the decrease in the percent viable cells after the treatment of MTX-GNPs, with an arrest in cell cycle at G0/G1 phase and a significant increase in apoptotic cell population and loss of mitochondrial membrane potential in MCF-7 and MDA-MB-231 cells. Folate receptor targeted MTX-GNPs showed significant cellular uptake in breast cancer cells along with significant down-regulation in expression of anti-apoptotic gene (Bcl-2) and up-regulation in expression of pro-apoptotic genes (Bax, Caspase-3, Caspase-9, APAF-1, p53). These results unveil the increased anti-cancer effect of MTX-GNPs in cancer cells. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13205-021-02718-7.

Nanotherapeutics for the Treatment of Cancer and Arthritis.

BACKGROUND: Nanotechnology is gaining significant attention worldwide for the treatment of complex diseases such as AIDS (acquired immune deficiency syndrome), cancer and rheumatoid arthritis. Nanomedicine is the application of nanotechnology used for diagnosis and treatment for the disease that includes the preservation and improvement of human health by covering an area such as drug delivery using nanocarriers, nanotheranostics and nanovaccinology. The present article provides an insight into several aspects of nanomedicine such as usages of multiple types of nanocarriers, their status, advantages and disadvantages with reference to cancer and rheumatoid arthritis. METHODS: An extensive search was performed on the bibliographic database for research article on nanotechnology and nanomedicine along with looking deeply into the aspects of these diseases, and how all of them are co-related. We further combined all the necessary information from various published articles and briefed to provide the current status. RESULTS: Nanomedicine confers a unique technology against complex diseases which includes early diagnosis, prevention, and personalized therapy. The most common nanocarriers used globally are liposomes, polymeric nanoparticles, dendrimers, metallic nanoparticles, magnetic nanoparticles, solid lipid nanoparticles, polymeric micelles and nanotubes among others. CONCLUSION: Nanocarriers are used to deliver drugs and biomolecules like proteins, antibody fragments, DNA fragments, and RNA fragments as the base of cancer biomarkers.

Formulation of vitamin D encapsulated cinnamon oil nanoemulsion: Its potential anti-cancerous activity in human alveolar carcinoma cells.

Cinnamon oil is used for medicinal purpose since ancient time because of its antioxidant activity. Oil-in-water nanoemulsion (NE) of cinnamon oil was formulated using cinnamon oil, nonionic surfactant Tween 80 and water by ultrasonication technique. Phase diagram was constructed to investigate the influence of oil, water and surfactant concentration. Vitamin D encapsulated cinnamon oil NE was fabricated by wash out method followed by ultrasonication in similar fashion. The hydrodynamic size of cinnamon oil NE and vitamin D encapsulated cinnamon oil NE was observed as 40.52 and 48.96 nm in complete DMEM F12 media respectively. We focused on the cytotoxic and genotoxic responses of NEs in A549 cells in concentration dependent manner. We observed that both NEs induce DNA damage along with corresponding increase in micronucleus frequency that is evident from the comet and CBMN assay. Both the NEs arrested the cell cycle progression in G0/G1 phase, showed increased expression of Bax, capase-3 and caspase-9 and decrease expression of BcL2 proteins along with significant (p < 0.05) increase in apoptotic cell population and loss of mitochondrial membrane potential. NEs were also evaluated for bactericidal efficacy against E. coli. Thus, both NEs have cytotoxic, genotoxic and antibacterial potential and hence can also be used in food industry with cinnamon oil as carrier for lipophilic nutraceutical like vitamin D.

Cellular internalization and antioxidant activity of cerium oxide nanoparticles in human monocytic leukemia cells.

Overproduction of free radicals contributes to oxidative stress and inflammation leading to various disease conditions. Cerium oxide nanoparticles (nanoceria) have been shown to scavenge free radicals and have the potential for being used as a therapeutic agent in disease conditions. Therefore, in the present study, human monocytic leukemia cells (THP-1) were used as a model to evaluate the uptake and free radical scavenging activity of nanoceria. Our data showed a significant (P<0.05) increase in the internalization of nanoceria in a concentration-dependent (10-100 µg/mL) manner in THP-1 cells. Although no cytotoxicity was observed at these concentrations, nanoceria significantly (P<0.05) reduced the amount of reactive oxygen species. This was evident by a significant (P<0.05) decrease in the 2,7-dichlorofluorescein diacetate fluorescence observed in flow cytometry and fluorescence microscopy. The present study shows that nanoceria have therapeutic potential in diseases such as cancer.

Curcumin Ag nanoconjugates for improved therapeutic effects in cancer.

Curcumin has a broad spectrum of pharmacological activities, one of them is anticancer activity that is mediated through multiple mechanisms. The major disadvantage associated with the use of curcumin is its low bioavailability due to its poor aqueous solubility. Nanoformulations of curcumin provide an effective solution for this problem. In this study, we have synthesized curcumin Ag nanoconjugates and evaluated their anticancer potential.

Synthesis of biocompatible iron oxide nanoparticles as a drug delivery vehicle.

Over the last decade, there has been growing interest in developing novel nanoparticles (NPs) for biomedical applications. A safe-by-design approach was used in this study to synthesize biocompatible iron oxide NPs. The size of the particles obtained was ~100 nm. Although these NPs were significantly (P<0.05) internalized in MCF-7 (human breast adenocarcinoma cell line) cells, no adverse effect was observed in the cells as assessed by cytotoxicity assays (neutral red uptake and 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) and cell cycle analysis. Our data demonstrate the potential of iron oxide NPs as a biocompatible carrier for targeted drug delivery.

Cell cycle dependent cellular uptake of zinc oxide nanoparticles in human epidermal cells.

Metal oxide nanoparticles (NPs), including zinc oxide (ZnO) NPs have shown success for use as vehicles for drug delivery and targeting gene delivery in many diseases like cancer. Current anticancer chemotherapeutics fail to effectively differentiate between cancerous and normal cells. There is an urgent need to develop novel drug delivery system that can better target cancer cells while sparing normal cells and tissues. Particularly, ZnO NPs exhibit a high degree of cancer cell selectivity and induce cell death, oxidative stress, interference with the cell cycle progression and genotoxicity in cancerous cells. In this scenario, effective cellular uptake of NP seems to be crucial, which is shown to be affected by cell cycle progression. In the present study, the cytotoxic potential of ZnO NPs and the effect of different cell cycle phases on the uptake of ZnO NPs were examined in A431 cells. It is shown that the ZnO NPs led to cell death and reactive oxygen species generation and were able to induce cell cycle arrest in S and G2/M phase with the higher uptake in G2/M phase compared with other phases.

TiO2 nanoparticles induce DNA double strand breaks and cell cycle arrest in human alveolar cells.

TiO2 nanoparticles (NPs) have the second highest global annual production (∼3000 tons) among the metal-containing NPs. These NPs are used as photocatalysts for bacterial disinfection, and in various other consumer products including sunscreen, food packaging, therapeutics, biosensors, surface cleaning agents, and others. Humans are exposed to these NPs during synthesis (laboratory), manufacture (industry), and use (consumer products, devices, medicines, etc.), as well as through environmental exposures (disposal). Hence, there is great concern regarding the health effects caused by exposure to NPs and, in particular, to TiO2 NPs. In the present study, the genotoxic potential of TiO2 NPs in A549 cells was examined, focusing on their potential to induce ROS, different types of DNA damage, and cell cycle arrest. We show that TiO2 NPs can induce DNA damage and a corresponding increase in micronucleus frequency, as evident from the comet and cytokinesis-block micronucleus assays. We demonstrate that DNA damage may be attributed to increased oxidative stress and ROS generation. Furthermore, genomic and proteomic analyses showed increased expression of ATM, P53, and CdC-2 and decreased expression of ATR, H2AX, and Cyclin B1 in A549 cells, suggesting induction of DNA double strand breaks. The occurrence of double strand breaks was correlated with cell cycle arrest in G2/M phase. Overall, the results indicate the potential for genotoxicity following exposure to these TiO2 NPs, suggesting that use should be carefully monitored.