A Bioinspired Flexible Sensor for Electrochemical Probing of Dynamic Redox Disequilibrium in Cancer Cells.

Malignant tumors pose a serious risk to human health. Ascorbic acid (AA) has potential for tumor therapy; however, the mechanism underlying the ability of AA to selectively kill tumor cells remains unclear. AA can cause redox disequilibrium in tumor cells, resulting in the release of abundant reactive oxygen species, represented by hydrogen peroxide (H2 O2 ). Therefore, the detection of H2 O2 changes can provide insight into the selective killing mechanism of AA against tumor cells. In this work, inspired by the ion-exchange mechanism in coral formation, a flexible H2 O2 sensor (PtNFs/CoPi@CC) is constructed to monitor the dynamics of H2 O2 in the cell microenvironment, which exhibits excellent sensitivity and spatiotemporal resolution. Moreover, the findings suggest that dehydroascorbic acid (DHA), the oxidation product of AA, is highly possible the substance that actually acts on tumor cells in AA therapy. Additionally, the intracellular redox disequilibrium and H2 O2 release caused by DHA are positively correlated with the abundance and activity of glucose transporter 1 (GLUT1). In conclusion, this work has revealed the potential mechanism underlying the ability of AA to selectively kill tumor cells through the construction and use of PtNFs/CoPi@CC. The findings provide new insights into the clinical application of AA.

A Novel Poly(3-hexylthiophene) Engineered Interface for Electrochemical Monitoring of Ascorbic Acid During the Occurrence of Glutamate-Induced Brain Cytotoxic Edemas.

Although neuroelectrochemical sensing technology offers unique benefits for neuroscience research, its application is limited by substantial interference in complex brain environments while ensuring biosafety requirements. In this study, we introduced poly(3-hexylthiophene) (P3HT) and nitrogen-doped multiwalled carbon nanotubes (N-MWCNTs) to construct a composite membrane-modified carbon fiber microelectrode (CFME/P3HT-N-MWCNTs) for ascorbic acid (AA) detection. The microelectrode presented good linearity, selectivity, stability, antifouling, and biocompatibility and exhibited great performance for application in neuroelectrochemical sensing. Subsequently, we applied CFME/P3HT-N-MWCNTs to monitor AA release from in vitro nerve cells, ex vivo brain slices, and in vivo living rat brains and determined that glutamate can induce cell edema and AA release. We also found that glutamate activated the N-methyl-d-aspartic acid receptor, which enhanced Na+ and Cl- inflow to induce osmotic stress, resulting in cytotoxic edema and ultimately AA release. This study is the first to observe the process of glutamate-induced brain cytotoxic edema with AA release and to reveal the mechanism. Our work can benefit the application of P3HT in in vivo implant microelectrode construction to monitor neurochemicals, understand the molecular basis of nervous system diseases, and discover certain biomarkers of brain diseases.

Aptamer functionalized cell membrane for brain and nerve cell sensing with high sensitivity and stability.

Accurate dopamine (DA) monitoring with high stability is essential for investigating the chemical basis of brain function and pathology. Electrochemical-based tissue-implantable carbon fiber electrodes (CFEs) show great potential in sensing the dynamics of neurochemicals at a sub-second timescale. However, their anti-fouling property, selectivity, and stability pose challenges. Here, we presented a novel strategy to enhance electrode biocompatibility and stability by modifying CFE with a chitosan (CS) film, brain cell membrane (M), and aptamer cholesterol amphiphiles (DNA-cho). We found that CFE was uniformly covered by a cicada-like membrane after being modified. Electrochemical characterizations indicated that DNA-cho-M-CS-CFE exhibited a wide linear range of DA concentration and showed high sensitivity, specificity, and stability. The electrode also presented excellent fouling resistance and biocompatibility. Moreover, the biosensor was used to detect DA in K+-induced brain slices and PC12 cells with a satisfactory stability and sensitivity and to prove that LPS treatment leads to the delayed and decreased release of DA. DNA-cho-M-CS-CFE showed excellent electrochemical performance and unique advantages for long-term in vivo sensing of living cells, thus providing a new feasible scheme for studying neurochemical kinetics and brain diseases.