Construction of a Bifunctional Nanoelectrode for Intracellular Natural Product Delivery and Monitoring Anticancer Efficiency in Single Cells.

Natural products play a significant role in new drug discovery and anticancer therapy, making the evaluation of their anticancer efficiency crucial for clinical application. However, delivering natural products to single cells and in situ monitoring of induced signaling molecule fluctuation to evaluate anticancer efficiency remain significant challenges. Hence, we proposed a universal and straightforward strategy to construct a bifunctional nanoelectrode that integrates drug loading and monitoring of signal molecule fluctuations at the single-cell level. Platinum (Pt) nanoparticles/reduced graphene oxide (rGO) composites were first electrochemically deposited on the carbon fiber nanoelectrode (CFNE@Pt/rGO) to serve as electrocatalytic materials for the monitoring of natural-product-induced reactive oxygen species (ROS) generation. The GO/natural product complex, formed by π-π stacking and hydrophobic interactions, was further electrochemically reduced on the surface of CFNE@Pt/rGO to enable the CFNE drug-loading function. Using this bifunctional functional nanoelectrode, a series of natural products (such as capsaicin, curcumin, and chrysin) were delivered into single cancer cells, and their anticancer efficiency was evaluated by measuring ROS generation. The results showed that intracellular ROS production induced by chrysin was 1.5-fold greater than that of curcumin and 2.1-fold greater than that of capsaicin. This work proposes an effective tool to evaluate the anticancer efficiency of various natural products. Additionally, this nanotool can be expanded to monitor the fluctuation of other biomolecules (such as RNS, GSH, NADH, etc.) by replacing Pt nanoparticles with other electrocatalytic materials, which is significant for comprehensively exploring the anticancer efficiency of new drugs and for the clinical treatment of various diseases.