PCL-based nanoparticles for doxorubicin-ezetimibe co-delivery: A combination therapy for prostate cancer using a drug repurposing strategy

Results: The average size of nanoparticles (NPs) observed by field emission scanning electron microscopy (FE-SEM) was around 82?23.80 nm, 59.7?18.7 nm, and 67.6?23.8 nm for EZ@ PCEC, DOX@PCEC, and DOX+EZ@PCEC NPs, respectively, which had a spherical morphology. Based on the MTT assay results, PCEC copolymer exhibited negligible cytotoxicity on the PC3 cell line. [...]PCEC was a biocompatible and suitable nano-vehicle for this study. In preclinical studies, not only statins, but also EZ, demonstrated antitumor activity in PCA cells and synergistic toxicity when combined with other anti-cancer drugs.12 Recently, repurposing the efficacy of the currently used anti-viral drugs, such as remdesivir and favipiravir, has attracted a lot of attention to fight COVID-19.13 Use of drug combinations could increase the success rate of drug repurposing screens. [...]a better knowledge of these therapeutic modalities is needed for improved cancer therapy14 Combination therapy based on nano codelivery is an effective method to overcome chemotherapy limitations. [...]the prepared copolymer was placed under the vacuum to evaporate the solvent and dry it.19 Preparation of drug-loaded PCEC NPs NPs were prepared using both double emulsion (W /O/ W2)21 and simple emulsion (O/W) methods (Fig.

Molecular Docking and Simulation Analysis of Cyclopeptides as Anticancer Agents

Background: Cancer is a leading cause of death for people worldwide, in addition to the rise in mortality rates attributed to the Covid epidemic. This allows scientists to do additional research. Here, we have selected Integerrimide A, cordy heptapeptide, and Oligotetrapeptide as the three cyclic proteins that will be further studied and investigated in this context.Methods: Docking research was carried out using the protein complexes 1FKB and 1YET, downloaded from the PDB database and used in the docking investigations. Cyclopeptides have been reported to bind molecularly to human HSP90 (Heat shock protein) and FK506. It was possible to locate HSP90 in Protein Data Banks 1YET and 1FKB. HSP90 was retrieved from Protein Data Bank 1YET and 1FKB. Based on these findings, it is possible that the anticancer effects of Int A, Cordy, and Oligo substances could be due to their ability to inhibit the mTOR rapamycin binding domain and the HSP90 Geldanamycin binding domain via the mTOR and mTOR chaperone pathways. During the calculation, there were three stages: system development, energy reduction, and molecular dynamics (also known as molecular dynamics). Each of the three compounds demonstrated a binding affinity for mTOR's Rapamycin binding site that ranged from -6.80 to -9.20 Kcal/mol (FKB12).Results: An inhibition constant Ki of 181.05 nM characterized Cordy A with the highest binding affinity (-9.20 Kcal/mol). Among the three tested compounds, Cordy A was selected for MD simulation. HCT116 and B16F10 cell lines were used to test each compound's anticancer efficacy. Doxorubicin was used as a standard drug. The cytotoxic activity of substances Int A, Cordy A, and Oligo on HCT116 cell lines was found to be 77.65 μM, 145.36 μM, and 175.54 μM when compared to Doxorubicin 48.63 μM, similarly utilizing B16F10 cell lines was found to be 68.63 μM, 127.63 μM, and 139.11 μM to Doxorubicin 45.25 μM.Conclusion: Compound Cordy A was more effective than any other cyclic peptides tested in this investigation.

Antibacterial and Antiviral Activities of Microwave-assisted Thuja orientalis Extracts

In this study, the components of microwave-assisted extracts obtained from Thuja orientalis leaves were analyzed, and the cytotoxicity, antibacterial and antiviral activities were evaluated. The predominant components from microwave-assisted extraction were catechin, leucopelargonidin, arecatannin, quinolone, and kaempferol derivatives, which are classified in the fla-vonoid and tannin groups. We observed that the 0.11 mg/mL of extract concentration did not show cytotoxicity in HaCaT cells. The antibacterial activities were tested according to the guidelines of methods for determining the bactericidal activity of antimicrobial agents. The extracts showed 99.9% antibacterial efficiency against gram-positive S. aureus, while the anti-bacterial effect on gram-negative E. coli was insignificant. When the extract concentration and contact time with bacteria were increased, 99.9% antibacterial efficiency was observed for E. coli as well as S. aureus. Following the standard to assess the activity of microbicides against viruses in suspension (ASTM-E1052-20), the antiviral efficiency was more than 99.99% for influenza A (H1N1) and SARS-CoV-2. These results suggest its potential use in antiviral disinfectants, surface coatings, personal protective equipment, and textiles. © 2023 The Korean Society of Industrial and Engineering Chemistry. All rights reserved.

Lysosomal nanotoxicity: Impact of nanomedicines on lysosomal function.

Although several nanomedicines got clinical approval over the past two decades, the clinical translation rate is relatively small so far. There are many post-surveillance withdrawals of nanomedicines caused by various safety issues. For successful clinical advancement of nanotechnology, it is of unmet need to realize cellular and molecular foundation of nanotoxicity. Current data suggest that lysosomal dysfunction caused by nanoparticles is emerging as the most common intracellular trigger of nanotoxicity. This review analyzes prospect mechanisms of lysosomal dysfunction-mediated toxicity induced by nanoparticles. We summarized and critically assessed adverse drug reactions of current clinically approved nanomedicines. Importantly, we show that physicochemical properties have great impact on nanoparticles interaction with cells, excretion route and kinetics, and subsequently on toxicity. We analyzed literature on adverse reactions of current nanomedicines and hypothesized that adverse reactions might be linked with lysosomal dysfunction caused by nanomedicines. Finally, from our analysis it becomes clear that it is unjustifiable to generalize safety and toxicity of nanoparticles, since different particles possess distinct toxicological properties. We propose that the biological mechanism of the disease progression and treatment should be central in the optimization of nanoparticle design.

SARS-CoV-2 Spike Expression at the Surface of Infected Primary Human Airway Epithelial Cells.

Different serological assays were rapidly generated to study humoral responses against the SARS-CoV-2 Spike glycoprotein. Due to the intrinsic difficulty of working with SARS-CoV-2 authentic virus, most serological assays use recombinant forms of the Spike glycoprotein or its receptor binding domain (RBD). Cell-based assays expressing different forms of the Spike, as well as pseudoviral assays, are also widely used. To evaluate whether these assays recapitulate findings generated when the Spike is expressed in its physiological context (at the surface of the infected primary cells), we developed an intracellular staining against the SARS-CoV-2 nucleocapsid (N) to distinguish infected from uninfected cells. Human airway epithelial cells (pAECs) were infected with authentic SARS-CoV-2 D614G or Alpha variants. We observed robust cell-surface expression of the SARS-CoV-2 Spike at the surface of the infected pAECs using the conformational-independent anti-S2 CV3-25 antibody. The infected cells were also readily recognized by plasma from convalescent and vaccinated individuals and correlated with several serological assays. This suggests that the antigenicity of the Spike present at the surface of the infected primary cells is maintained in serological assays involving expression of the native full-length Spike.