Construction\nof a Bifunctional Nanoelectrode for Intracellular\nNatural Product Delivery and Monitoring Anticancer Efficiency in Single\nCells

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