Bioengineering a Light-Responsive Encapsulin Nanoreactor: A Potential Tool for In Vitro Photodynamic Therapy

Encapsulins, a prokaryotic class of self-assembling protein nanocompartments, are being re-engineered to serve as nanoreactors for the augmentation or creation of key biochemical reactions. However, approaches that allow encapsulin nanoreactors to be functionally activated with spatial and temporal precision are lacking. We report the construction of a light-responsive encapsulin nanoreactor for on demand production of reactive oxygen species (ROS). Herein, encapsulins were loaded with the fluorescent flavoprotein mini-singlet oxygen generator (miniSOG), a biological photosensitizer that is activated by blue light to generate ROS, primarily singlet oxygen (O-1(2)). We established that the nanocompartments stably encased miniSOG and in response to blue light were able to mediate the photoconversion of molecular oxygen into ROS. Using an in vitro model of lung cancer, we showed that ROS generated by the nanoreactor triggered photosensitized oxidation reactions which exerted a toxic effect on tumor cells, suggesting utility in photodynamic therapy. This encapsulin nanoreactor thus represents a platform for the light-controlled initiation and/or modulation of ROS-driven processes in biomedicine and biotechnology.

Automated summary

Encapsulins, a class of self-assembling protein nanocompartments, have been re-engineered to serve as nanoreactors for the production of reactive oxygen species (ROS) through light-responsive activation. This light-controlled encapsulin nanoreactor shows potential in triggering photosensitized oxidation reactions in tumor cells, highlighting its utility in photodynamic therapy in biomedicine and biotechnology.