2 research outputs found
In Vitro and In Vivo Demonstration of Human-Ovarian-Cancer Necrosis through a Water-Soluble and Near-Infrared-Absorbing Chlorin
With
the objective of developing efficient sensitizers for therapeutic
applications, we synthesized a water-soluble 5,10,15,20-tetrakis(3,4-dihydroxyphenyl)chlorin
(TDC) and investigated its in vitro and in vivo biological efficacy,
comparing it with the commercially available sensitizers. TDC showed
high water solubility (6-fold) when compared with that of Foscan and
exhibited excellent triplet-excited-state (84%) and singlet-oxygen
(80%) yields. In vitro photobiological investigations in human-ovarian-cancer
cell lines SKOV-3 showed high photocytotoxicity, negligible dark toxicity,
rapid cellular uptake, and specific localization of TDC in neoplastic
cells as assessed by flow-cytometric cell-cycle and propidium iodide
staining analysis. The photodynamic effects of TDC include confirmed
reactive-oxygen-species-induced mitochondrial damage leading to necrosis
in SKOV-3 cell lines. The in vivo photodynamic activity in nude-mouse
models demonstrated abrogation of tumor growth without any detectable
pathology in the skin, liver, spleen, or kidney, thereby demonstrating
TDC application as an efficient and safe photosensitizer
<i>In Vitro</i> Demonstration of Apoptosis Mediated Photodynamic Activity and NIR Nucleus Imaging through a Novel Porphyrin
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