Intracellular Hyperbranched Polymerization for Circumventing Cancer Drug Resistance

Polymerization inside living cells provides chemists with a multitude of possibilities to modulate cell activities. Considering the advantages of hyperbranched polymers, such as a large surface area for target sites and multilevel branched structures for resistance to the efflux effect, we reported a hyperbranched polymerization in living cells based on the oxidative polymerization of organotellurides and intracellular redox environment. The intracellular hyperbranched polymerization was triggered by reactive oxygen species (ROS) in the intracellular redox microenvironment, effectively disrupting antioxidant systems in cells by an interaction between Te (+4) and selenoproteins, thus inducing selective apoptosis of cancer cells. Importantly, the obtained hyperbranched polymer aggregated into branched nanostructures in cells, which could effectively evade drug pumps and decrease drug efflux, ensuring the polymerization for persistent treatment. Finally, in vitro and in vivo studies confirmed that our strategy presented selective anticancer efficacy and well biosafety. This approach provides a way for intracellular polymerization with desirable biological applications to regulate cell activities.