In Situ Silver-based Electrochemical Bioreactor In Vivo

Abstract In this study we show for the first time that a reduced graphene oxide (rGO) carrier has a 15-fold higher catalysis rate than graphene oxide (GO) in Ag+ reduction. Based on this, we constructed a tumor microenvironment-enabled in situ silver-based electrochemical oncolytic bioreactor (SEOB) which unlocked an Ag+ prodrug to generate silver nanoparticles and inhibited the growth of various tumors. In this bioreactor system, intratumoral H2O2 acted as the reductant and the rGO carrier acted as the catalyst. Chelation of aptamers to this prodrug increased the production of silver nanoparticles by tumor cells, especially in the presence of Vitamin C, which broke down in tumor cells to supply massive amounts of H2O2. Consequently, highly efficient silver nanoparticle-induced apoptosis was observed in HepG2 and A549 cells in vitro and in HepG2- and A549-derived tumors in vivo. The apoptosis was associated with ROS-induced changes in mitochondrial membrane potential and DNA damage. The specific aptamer targeting and intratumoral silver nanoparticle production guaranteed excellent biosafety, with no damage to normal cells, because the Ag+ prodrug was specifically unlocked in tumors. More significantly, there was no evident tissue damage in monkeys, which greatly increases the clinical translation potential of the SEOB system.