Abstract
Photodynamic therapy (PDT) is a clinical treatment for cancer or non-neoplastic diseases, and the photosensitizers (PSs) are crucial for PDT efficiency. The commonly used chemical PSs, generally produce ROS through the type II reaction that highly relies on the local oxygen concentration. However, the hypoxic tumor microenvironment and unavoidable dark toxicity of PSs greatly restrain the wide application of PDT. The genetically encoded PSs, unlike chemical PSs, can be modified using genetic engineering techniques and targeted to unique cellular compartments, even within a single cell. KillerRed, as a dimeric red fluorescent protein, can be activated by visible light or upconversion luminescence to execute the Type I reaction of PDT, which does not need too much oxygen and surely attract the researchers’ focus. In particular, nanotechnology provides new opportunities for various modifications of KillerRed and versatile delivery strategies. This review more comprehensively outlines the applications of KillerRed, highlighting the fascinating features of KillerRed genes and proteins in the photodynamic systems. Furthermore, the advantages and defects of KillerRed are also discussed, either alone or in combination with other therapies. These overviews may facilitate understanding KillerRed progress in PDT and suggest some emerging potentials to circumvent challenges to improve the efficiency and accuracy of PDT.
Highlights
One research has indicated that mitochondria-targeted KillerRed and membrane-targeted KillerRed (mem-KR) function through two different pathways: Photoactivated mt-KR resulted in organelle fragmentation without killing the cells, while mem-KR caused cell death via lipid peroxidation [38]
reactive oxygen species (ROS) generated from nucleus-targeted KillerRed can directly cause DNA damage with precise temporal and spatial control when compared to chemical PSs
The results shows that after irradiation with NIR light (980 nm, 0.5 W/cm2, 30 min), The results shows that after irradiation with NIR light (980 nm, 0.5 W/cm2, 30 min), the efficacy of Photodynamic therapy (PDT) with KR-upconversion nanoparticles nanoparticles (UCNPs) can reach about 70% at approximately 1cm tissue the efficacy of PDT with KR-UCNP can reach about 70% at approximately 1cm tissue depth, while KillerRed only can just achieve about 7% [85]
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. The contributions of type I and type II mechanisms are affected by a variety of factors including pH value, tissue dielectric constant, oxygen concentration, and the properties of PSs. Since PDT can rapidly consume lots of tissue oxygen and shut down the blood vessels that deliver oxygen, the treatment may induce more serious hypoxia in tumor environment [8]. To further develop the functions and applications of KillerRed, will focus on the structure, reaction mechanism, and physiological function of KillerRed as both endogenous and exogenous PS for cancer therapeutics and imaging. The phototoxicity this review will focus on the structure, reaction mechanism, and physiological function of KillerRed as both endogenous and exogenous PS for cancer therapeutics and imaging.
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