<i>In Vitro</i> Demonstration of Apoptosis
Mediated Photodynamic Activity and NIR Nucleus Imaging through a Novel
Porphyrin
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Abstract
We synthesized a novel water-soluble porphyrin <b>THPP</b> and its metalated derivative <b>Zn-THPP</b> having
excellent
triplet excited state quantum yields and singlet oxygen generation
efficiency. When compared to U.S. Food and Drug Administration approved
and clinically used sensitizer Photofrin, <b>THPP</b> showed <i>ca.</i> 2–3-fold higher <i>in vitro</i> photodynamic
activity in different cell lines under identical conditions. The mechanism
of the biological activity of these porphyrin systems has been evaluated
through a variety of techniques: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
bromide (MTT) assay, comet assay, poly(ADP-ribose)polymerase (PARP)
cleavage, CM-H<sub>2</sub>DCFDA assay, DNA fragmentation, flow cytometric
analysis, fluorescence, and confocal microscopy, which confirm the
apoptotic cell death through predominantly reactive oxygen species
(ROS). Moreover, <b>THPP</b> showed rapid cellular uptake and
are localized in the nucleus of the cells as compared to Hoechst dye
and Photofrin, thereby demonstrating its use as an efficient sensitizer
in photodynamic therapy and live cell NIR nucleus imaging applications