2D materials in electrochemical sensors for in vitro or in vivo use.

Individual cells and cell populations are at the present time investigated with a myriad of analytical tools. While most of them are commercially available, some of these analytical tools are just emerging from research laboratories and are in the developmental phase. Electrochemical sensors which allow the monitoring of low molecular weight compounds released (and / or uptaken) by cells are among these emerging tools. Such sensors are increasingly built using 2D materials (e.g. graphene-based materials, transition metal dichalcogenides, etc.) with the aim of conferring better analytical performances to these devices. The present work critically reviews studies published during the last 10 years describing electrochemical sensors made with 2D materials and exploited to monitor small compounds (e.g. H2O2, ·NO, glucose, etc.) in living biological systems. It also discusses the very few 2D material-based electrochemical sensors which are wearable or usable in vivo. Finally, the present work includes a specific section about 2D material biocompatibility, a fundamental requirement for 2D material-based sensor applications in vitro and in vivo. As such, the review provides a critical view on the state of the art of electrochemical sensors made with 2D materials and used at cellular level and it evaluates the possibility that such sensors will be used on / in the human body on a wider scale.

Restoring microenvironmental redox and pH homeostasis inhibits neoplastic cell growth and migration: therapeutic efficacy of esomeprazole plus sulfasalazine on 3-MCA-induced sarcoma.

Neoplastic cells live in a stressful context and survive thanks to their ability to overcome stress. Thus, tumor cell responses to stress are potential therapeutic targets. We selected two such responses in melanoma and sarcoma cells: the xc- antioxidant system, that opposes oxidative stress, and surface v-ATPases that counteract the low pHi by extruding protons, and targeted them with the xc- blocker sulfasalazine and the proton pump inhibitor esomeprazole. Sulfasalazine inhibited the cystine/cysteine redox cycle and esomeprazole decreased pHi while increasing pHe in tumor cell lines. Although the single treatment with either drug slightly inhibited cell proliferation and motility, the association of sulfasalazine and esomeprazole powerfully decreased sarcoma and melanoma growth and migration. In the 3-methylcholanthrene (3-MCA)-induced sarcoma model, the combined therapy strongly reduced the tumor burden and increased the survival time: notably, 22 % of double-treated mice recovered and survived off therapy. Tumor-associated macrophages (TAM) displaying M2 markers, that abundantly infiltrate sarcoma and melanoma, overexpress xc- and membrane v-ATPases and were drastically decreased in tumors from mice undergone the combined therapy. Thus, the double targeting of tumor cells and macrophages by sulfasalazine and esomeprazole has a double therapeutic effect, as decreasing TAM infiltration deprives tumor cells of a crucial allied. Sulfasalazine and esomeprazole may therefore display unexpected therapeutic values, especially in case of hard-to-treat cancers.