High biocompatible FITC-conjugated silica nanoparticles for cell labeling in both in vitro and in vivo models.

Fluorescence nanosilica-based cell tracker has been explored and applied in cell biological research. However, the aggregation of these nanoparticles at physiological pH is still the main limitation. In this research, we introduced a novel fluorescence nano-based cell tracker suitable for application in live cells. The silica-coated fluorescein isothiocyanate isomer (FITC-SiO2) nanoparticles (NPs) were modified with carboxymethylsilanetriol disodium salt (FITC-SiO2-COOH), integrating the dianion form of FITC molecules. This nanosystem exhibited superior dispersion in aqueous solutions and effectively mitigated dye leakage. These labeled NPs displayed notable biocompatibility and minimal cytotoxicity in both in vitro and in vivo conditions. Significantly, the NPs did not have negative implications on cell migration or angiogenesis. They successfully penetrated primary fibroblasts, human umbilical vein endothelial cells and HeLa cells in both 2D and 3D cultures, with the fluorescence signal enduring for over 72 h. Furthermore, the NP signals were consistently observed in the developing gastrointestinal tract of live medaka fish larvae for extended periods during phases of subdued digestive activity, without manifesting any apparent acute toxicity. These results underscore the promising utility of FITC-SiO2-COOH NPs as advanced live cell trackers in biological research.

Detection of sFas, sCD137, and IL-27 Cytokines as Potential Biomarkers for Hepatocellular Carcinoma Diagnosis.

Purpose: Hepatocellular carcinoma (HCC), a prevalent type of liver cancer, is mainly diagnosed in the advanced stage, leading to a high mortality rate. Recent advances have identified peripheral cytokines as a potential tool to predict disease outcomes and inform therapeutic decisions. Hence, in this study, we aim to build a predictive model for HCC based on serum levels of different cytokines. Patients and Methods: We used immunoassay to quantify the concentrations of IL-27, MIP-1ß, Perforin, sCD137, sFas, and TNF-α in the serum of 38 HCC patients and 15 healthy controls. Logistic regression was then used to construct classification models detecting HCC based on these cytokines. A nomogram of the best-performing model was generated to visualize HCC prediction. Results: sFas and MIP-1ß were found to be significantly higher in HCC patients compared to controls. Predictive models based on cytokine levels combining sFas, sCD137, and IL-27 performed the best in distinguishing HCC patients from healthy controls. This model has a bias-corrected area under the receiver operating characteristic (ROC) curve (AUC) of 0.948, a sensitivity of 92.11%, a specificity of 93.33%, and an accuracy of 0.925. Conclusion: Our findings suggest that serum cytokines have the potential to be utilized in HCC screening to improve detection rates.

High Biocompatibility, MRI Enhancement, and Dual Chemo- and Thermal-Therapy of Curcumin-Encapsulated Alginate/Fe3O4 Nanoparticles.

(1) Background: Magnetite (Fe3O4) nanoparticles have great potential for biomedical applications, including hyperthermia and magnetic resonance imaging. In this study, we aimed to identify the biological activity of nanoconjugates composed of superparamagnetic Fe3O4 nanoparticles coated with alginate and curcumin (Fe3O4/Cur@ALG) in cancer cells. (2) Methods: The nanoparticles were evaluated for the biocompatibility and toxicity on mice. The MRI enhancement and hyperthermia capacities of Fe3O4/Cur@ALG were determined in both in vitro and in vivo sarcoma models. (3) Results: The results show that the magnetite nanoparticles exhibit high biocompatibility and low toxicity in mice at Fe3O4 concentrations up to 120 mg/kg when administered via intravenous injection. The Fe3O4/Cur@ALG nanoparticles enhance the magnetic resonance imaging contrast in cell cultures and tumor-bearing Swiss mice. The autofluorescence of curcumin also allowed us to observe the penetration of the nanoparticles into sarcoma 180 cells. In particular, the nanoconjugates synergistically inhibit the growth of sarcoma 180 tumors via magnetic heating and the anticancer effects of curcumin, both in vitro and in vivo. (4) Conclusions: Our study reveals that Fe3O4/Cur@ALG has a high potential for medicinal applications and should be further developed for cancer diagnosis and treatment.

In vitro high throughput screening, what next? Lessons from the screening for aurora kinase inhibitors.

Based on in vitro assays, we performed a High Throughput Screening (HTS) to identify kinase inhibitors among 10,000 small chemical compounds. In this didactic paper, we describe step-by-step the approach to validate the hits as well as the major pitfalls encountered in the development of active molecules. We propose a decision tree that could be adapted to most in vitro HTS.

Benzo[e]pyridoindoles, novel inhibitors of the aurora kinases.

Aurora kinases are serine/threonine protein kinases that are involved in cancer development and are important targets for cancer therapy. By high throughput screening of a chemical library we found that benzo[e]pyridoindole derivatives inhibited Aurora kinase. The most potent compound (compound 1) was found to be an ATP competitive inhibitor, which inhibited in vitro Aurora kinases at the nanomolar range. It prevented, ex vivo, the phosphorylation of Histone H3, induced mitosis exit without chromosome segregation, known phenomena observed upon Aurora B inactivation. This compound was also shown to affect the localization of Aurora B, since in the presence of the inhibitor the enzyme was delocalized on the whole chromosomes and remained associated with the chromatin of newly formed nuclei. In addition, compound 1 inhibited the growth of different cell lines derived from different carcinoma. Its IC(50) for H358 NSCLC (Non Small Cancer Lung Cells), the most sensitive cell line, was 145 nM. Furthermore compound 1 was found to be efficient towards multicellular tumor spheroid growth. It exhibited minimal toxicity in mice while it had some potency towards aggressive NSCLC tumors. Benzo[e]pyridoindoles represent thus a potential new lead for the development of Aurora kinase inhibitors.

[Survivin, the starlet of the passenger-protein complex : check-up for its tenth anniversary]. / Survivine, la petite reine du complexe passager : chek-up pour son dixième anniversaire.

Ten year after its discovery Survivin has gained a strategic place within the chromosomal passenger complex. Whereas INCENP, Borealin and Aurora B are fully immobile in the complex, Survivin is mobile on centromere. Its mobility is regulated both by phosphorylation and ubiquitination. Survivin is a dynamic messenger that senses the central spindle tension and participates to the control of the mitotic chekpoint. In this review, we have detailed the multiple mitotic activities of Survivin and discussed them in light of the recent reported crystallographic data.