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.

Selenium-Containing Nanoparticles Combine the NK Cells Mediated Immunotherapy with Radiotherapy and Chemotherapy.

Considering the limited clinical benefits of individual approaches against malignancy, natural killer (NK) cell-mediated immunotherapy is increasingly utilized in combination with radiotherapy and target therapeutics. However, the interplay of targeted agents, immunotherapy, and radiotherapy is complex. An improved understanding of the effect of chemotherapy or radiotherapy on specific molecular pathways in immune cells would help to optimize the synergistic antitumor efficiency. In this study, the selenium-containing nanoparticles (NPs) could deliver the chemotherapeutic drug doxorubicin (DOX) to tumor sites by systemic administration. Radiation stimuli facilitate DOX release and enhance chemotherapy efficiency. Moreover, radiation could oxidize diselenide-containing NPs to seleninic acid, which have both synergistic antitumor effect and immunomodulatory activity through enhancing NK cells function. These results indicate that the selenium-containing NPs would be a potential approach to achieve simultaneous treatments of immunotherapy, chemotherapy, and radiotherapy by a simple but effective method.