| Autor: |
Maffeis V; Department of Chemistry, University of Basel, Mattenstrasse 22, 4002 Basel, Switzerland.; NCCR-Molecular Systems Engineering, 4002 Basel, Switzerland., Skowicki M; Department of Chemistry, University of Basel, Mattenstrasse 22, 4002 Basel, Switzerland.; NCCR-Molecular Systems Engineering, 4002 Basel, Switzerland., Wolf KMP; NCCR-Molecular Systems Engineering, 4002 Basel, Switzerland.; Laboratory of Applied Mechanobiology, Institute of Translational Medicine, Department of Health Sciences and Technology, ETH Zurich, 8092 Zurich, Switzerland., Chami M; BioEM lab, Biozentrum, University of Basel, 4056 Basel, Switzerland., Schoenenberger CA; Department of Chemistry, University of Basel, Mattenstrasse 22, 4002 Basel, Switzerland., Vogel V; NCCR-Molecular Systems Engineering, 4002 Basel, Switzerland.; Laboratory of Applied Mechanobiology, Institute of Translational Medicine, Department of Health Sciences and Technology, ETH Zurich, 8092 Zurich, Switzerland., Palivan CG; Department of Chemistry, University of Basel, Mattenstrasse 22, 4002 Basel, Switzerland.; NCCR-Molecular Systems Engineering, 4002 Basel, Switzerland. |
| Abstrakt: |
Artificial organelles (AnOs) are in the spotlight as systems to supplement biochemical pathways in cells. While polymersome-based artificial organelles containing enzymes to reduce reactive oxygen species (ROS) are known, applications requiring control of their enzymatic activity and cell-targeting to promote intracellular ROS detoxification are underexplored. Here, we introduce advanced AnOs where the chemical composition of the membrane supports the insertion of pore-forming melittin, enabling molecular exchange between the AnO cavity and the environment, while the encapsulated lactoperoxidase (LPO) maintains its catalytic function. We show that H 2 O 2 outside AnOs penetrates through the melittin pores and is rapidly degraded by the encapsulated enzyme. As surface attachment of cell-penetrating peptides facilitates AnOs uptake by cells, electron spin resonance revealed a remarkable enhancement in intracellular ROS detoxification by these cell-targeted AnOs compared to nontargeted AnOs, thereby opening new avenues for a significant reduction of oxidative stress in cells. |
