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A genetically-encoded KillerRed protein as an intrinsically generated photosensitizer for photodynamic therapy

Paper ID Volume ID Publish Year Pages File Format Full-Text
6240 468 2014 9 PDF Available
Title
A genetically-encoded KillerRed protein as an intrinsically generated photosensitizer for photodynamic therapy
Abstract

Photodynamic therapy (PDT) has received considerable attention as a therapeutic treatment for cancer and other diseases; however, it is frequently accompanied by prolonged phototoxic reaction of the skin due to slow clearance of synthetic photosensitizers (PSs) administered externally. This study was designed to investigate the genetic use of pKillerRed-mem, delivered using complexes of chitosan (CS) and poly(γ-glutamic acid) (γPGA), to intracellularly express a membrane-targeted KillerRed protein that can be used as a potential PS for PDT. Following transfection with CS/pKillerRed/γPGA complexes, a red fluorescence protein of KillerRed was clearly seen at the cellular membranes. When exposed to green-light irradiation, the KillerRed-positive cells produced an excessive amount of reactive oxygen species (ROS) in a time-dependent manner. Data from viability assays indicate that ROS have an important role in mediating KillerRed-induced cytotoxicity, apoptosis, and anti-proliferation, suggesting that KillerRed can be used as an intrinsically generated PS for PDT treatments. Notably, the phototoxic reaction of KillerRed toward cells gradually became negligible over time, presumably because of its intracellular degradability. These experimental results demonstrate that this genetically encoded KillerRed is biodegradable and has potential for PDT-induced destruction of diseased cells.

Keywords
Photocytotoxicity; Degradable photosensitizer; Fluorescence protein; Gene therapy; Reactive oxygen species
First Page Preview
A genetically-encoded KillerRed protein as an intrinsically generated photosensitizer for photodynamic therapy
Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 35, Issue 1, January 2014, Pages 500–508
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering