Batch Effect Adjustment to Lower the Drug Attrition Rate of MCF-7 Breast Cancer Cells Exposed to Silica Nanomaterial-Derived Scaffolds.

Drug attrition rate is the calculation or measure of the clinical efficacy of a candidate drug on a screen platform for a specific period. Determining the attrition rate of a prospective cancer drug is a reliable way of testing the clinical efficacy. A low attrition rate in the last phase of a preclinical trial increases the success of a drug discovery process. It has been reported that the attrition rates of antineoplastic drugs are much higher than for other therapeutic drugs. Among the factors identified for the high attrition rates in antineoplastic drugs are the nature of the screen-based platforms involving human-derived xenografts, extracellular matrix-derived scaffold systems, and the synthetic scaffolds, which all have propensity to proliferate tumor cells at faster rates than in vivo primary tumors. Other factors that affect the high attrition rates are induced scaffold toxicity and the use of assays that are irrelevant, yet affect data processing. These factors contribute to the wide variation in data and systematic errors. As a result, it becomes imperative to filter batch variations and to standardize the data. Importantly, understanding the interplay between the biological milieu and scaffold connections is also crucial. Here the cell viability of MCF-7 (breast cancer cell line) cells exposed to different scaffolds were screened before cisplatin dosing using the calculated p-values. The statistical significance (p-value) of data was calculated using the one-way analysis of variance, with the p-value set as: 0 < p < 0.06. In addition, the half-maximal inhibitory concentration (IC50) of the different scaffolds exposed to MCF-7 cells were calculated with the probit extension model and cumulative distribution (%) of the extension data. The chemotherapeutic dose (cisplatin, 56 mg/m2) reduced the cell viability of MCF-7 cells to 5% within 24 h on the scaffold developed from silica nanoparticles (SNPs) and polyethylene glycol (PEG) formulation (SNP:PEG) mixtures with a ratio of 1:10, respectively.

Profiling the Neoplasm Microenvironment of Silica Nanomaterial-Derived Scaffolds of Single, 2-, and 3-Composite Systems.

The challenges with scaffold profiling of cell-based assay includes accelerated cancer cell proliferation, induced scaffold toxicity, and identifying irrelevant cancer cell-based assays in batch assessments. This study investigates profiling carcinoma of breast cancer cells of MCF-7 model systems using silica nanoparticles scaffold sourced from synthetic materials and plant extracts. Herein, the engineered tissue scaffolds were used to create temporary structures for cancer cell attachments, differentiation, and subsequently to assess the metabolic activity of the cancer cell colonies. The cell viability of the cancer cells was assessed using the tetrazolium compound (MTS reagent), which was reduced to colored formazan, to indicate metabolically active cancer cells in a proliferating assay. We aimed to develop cancer cell-based scaffolds that not only mimic the neoplastic activity, but that also allowed synergistic interaction with cisplatin for in vitro assay screening.

Combating Antibiotic-Resistant Gram-Negative Bacteria Strains with Tetracycline-Conjugated Carbon Nanoparticles.

Nontoxic carbon nanoparticle samples prepared by both bottom-up and top-down approaches do not inhibit Gram-negative bacterial growth, indicating excellent biocompatibilities. However, cell growth inhibitory efficacies increase considerably when the carbon nanoparticles are conjugated with the antibiotic tetracycline. In tetracycline-resistant bacteria, these efficacies can approach tenfold higher activities when compared to tetracycline alone. No structural abnormality such as membrane disruptions is evident in the tested bacterial strains; this is in contrast with other nanocarbon systems such as graphene oxides, carbon nanotubes, and amine-functionalized carbon nanoparticles which do exhibit membrane disruptions. In comparison, the tetracycline-conjugated carbon nanoparticles induce membrane perturbations (but not membrane disruptions), inhibiting bacterial efflux mechanisms. It is proposed that when tetracycline is conjugated to the surface of carbon nanoparticles, it functions to direct the nanoparticles to membrane-associated tetracycline efflux pumps, thereby blocking and subsequently inhibiting their function. The conjugation between biocompatible carbon nanoparticles and subtherapeutic but well-established antibiotic molecules may provide hybrid antibiotic assembly strategies resulting in effective multidrug efflux inhibition for combating antibiotic resistance.

Inhibition of Shewanella spp. growth by Syzygium australe and Syzygium luehmannii extracts: natural methods for the prevention of fish spoilage.

Syzygium australe and Syzygium luehmannii fruit and leaf were investigated for their ability to inhibit Shewanella spp. growth. Extracts of both Syzygium spp. displayed potent growth inhibitory properties against all Shewanella spp. tested in disc diffusion and liquid diffusion assays. In general, S. australe extracts were more potent inhibitors of Shewanella spp. growth, and the fruit extracts were generally better than the corresponding leaf extracts. The methanolic S. australe fruit extract was a particularly potent inhibitor of all Shewanella spp. growth, with MIC values as low as 87 µg/mL. The aqueous and ethyl acetate S. australe fruit extracts were similarly potent inhibitors of Shewanella spp. growth, albeit with slightly higher MIC values. Several other Syzygium spp. extracts also were potent bacterial growth inhibitors, albeit with MIC values generally >1000 µg/mL. The most potent S. australe fruit extracts were nontoxic in the Artemia franciscana bioassay, with LC50 values substantially >1000 µg/mL. The potent bacterial growth inhibitory activity and lack of toxicity of the S. australe fruit extracts indicate their potential as natural fish and seafood preservatives.