58 research outputs found
Conjugation to the Cell-Penetrating Peptide TAT Potentiates the Photodynamic Effect of Carboxytetramethylrhodamine
Cell-penetrating peptides (CPPs) can transport macromolecular cargos into live cells. However, the cellular delivery efficiency of these reagents is often suboptimal because CPP-cargo conjugates typically remain trapped inside endosomes. Interestingly, irradiation of fluorescently labeled CPPs with light increases the release of the peptide and its cargos into the cytosol. However, the mechanism of this phenomenon is not clear. Here we investigate the molecular basis of the photo-induced endosomolytic activity of the prototypical CPPs TAT labeled to the fluorophore 5(6)-carboxytetramethylrhodamine (TMR).We report that TMR-TAT acts as a photosensitizer that can destroy membranes. TMR-TAT escapes from endosomes after exposure to moderate light doses. However, this is also accompanied by loss of plasma membrane integrity, membrane blebbing, and cell-death. In addition, the peptide causes the destruction of cells when applied extracellularly and also triggers the photohemolysis of red blood cells. These photolytic and photocytotoxic effects were inhibited by hydrophobic singlet oxygen quenchers but not by hydrophilic quenchers.Together, these results suggest that TAT can convert an innocuous fluorophore such as TMR into a potent photolytic agent. This effect involves the targeting of the fluorophore to cellular membranes and the production of singlet oxygen within the hydrophobic environment of the membranes. Our findings may be relevant for the design of reagents with photo-induced endosomolytic activity. The photocytotoxicity exhibited by TMR-TAT also suggests that CPP-chromophore conjugates could aid the development of novel Photodynamic Therapy agents
Facilitating Understanding of Movements in Dynamic Visualizations: an Embodied Perspective
PHOTOOXIDATION OF CELL MEMBRANES USING EOSIN DERIVATIVES THAT LOCATE IN LIPID OR PROTEIN TO STUDY THE ROLE OF DIFFUSIBLE INTERMEDIATES
PHOTOMODIFICATION OF HUMAN ERYTHROCYTES: EXTERNAL HEAVY ATOM EFFECT, SELECTIVE PERMEABILITY AND PROPERTIES OF THE ANION PERMEATION PATHWAY
MEMBRANE IONIC CURRENT PHOTOMODIFICATION BY ROSE BENGAL and MENADIONE: ROLE OF SINGLET OXYGEN
Molecular Mechanisms of Photosensitization Induced by Drugs XII. Photochemistry and Photosensitization of Rufloxacin: An Unusual Photodegradation Path for the Antibacterials Containing a Fluoroquinolone-like Chromophore
MEMBRANE IONIC CURRENT PHOTOMODIFICATION BY ROSE BENGAL AND MENADIONE: ROLE OF SINGLET OXYGEN
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