14 April 2014 Increased efficacy of photodynamic therapy via sequential targeting
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Abstract
Photokilling depends on the generation of death signals after photosensitized cells are irradiated. A variety of intracellular organelles can be targeted for photodamage, often with a high degree of specificity. We have discovered that a low level of photodamage directed against lysosomes can sensitize both a murine hepatoma cell line (in 2D culture) and an inflammatory breast cancer line of human origin (in a 3D model) to subsequent photodamage directed at mitochondria. Additional studies were carried out with hepatoma cells to explore possible mechanisms. The phototoxic effect of the ‘sequential targeting’ approach was associated with an increased apoptotic response. The low level of lysosomal photodamage did not lead to any detectable migration of Fe++ from lysosomes to mitochondria or increased reactive oxygen species (ROS) formation after subsequent mitochondrial photodamage. Instead, there appears to be a signal generated that can amplify the pro-apoptotic effect of subsequent mitochondrial photodamage.
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David Kessel, David Kessel, Neha Aggarwal, Neha Aggarwal, Bonnie F. Sloane, Bonnie F. Sloane, } "Increased efficacy of photodynamic therapy via sequential targeting", Proc. SPIE 8931, Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy XXIII, 893102 (14 April 2014); doi: 10.1117/12.2042421; https://doi.org/10.1117/12.2042421
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