Intracellular Hyperbranched Polymerization for Circumventing Cancer Drug Resistance

Polymerization inside living cells provides chemistswith a multitudeof possibilities to modulate cell activities. Considering the advantagesof hyperbranched polymers, such as a large surface area for targetsites and multilevel branched structures for resistance to the effluxeffect, we reported a hyperbranched polymerization in living cellsbased on the oxidative polymerization of organotellurides and intracellularredox environment. The intracellular hyperbranched polymerizationwas triggered by reactive oxygen species (ROS) in the intracellularredox microenvironment, effectively disrupting antioxidant systemsin cells by an interaction between Te (+4) and selenoproteins, thusinducing selective apoptosis of cancer cells. Importantly, the obtainedhyperbranched 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 confirmedthat our strategy presented selective anticancer efficacy and wellbiosafety. This approach provides a way for intracellular polymerizationwith desirable biological applications to regulate cell activities.

Automated summary

Polymerization inside living cells provides chemists with a multitude of possibilities to modulate cell activities. We reported a hyperbranched polymerization in living cells based on the oxidative polymerization of organotellurides and intracellular redox environment. 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.