Abstract:
Photodynamic therapy (PDT) is an emerging treatment modality that employs the
photochemical interaction of three components. These are light of suitable wavelength,
photosensitizer, and singlet oxygen. The main objective of this work is the determination of
pharmacokinetics of different photosensitizers after laser irradiation in different biological
samples like cell lines and tissues to improve the efficacy of PDT. Present study investigates
the dynamic behaviour of different photosensitizers under laser irradiation e.g. (a)
biodistribution of Photofrin® (b) laser induced effects (c) depth of necrosis under exposure of
different wavelengths of light sources (d) synergistic effect of toxicity of ZnO nanostructures
bare and conjugated with photosensitizers like Aminolevulinic acid (5-ALA), Photofrin® and
protoporphyrin dimethyl ester (PPDME) determined for the treatment of localized cancer
cells.
Firstly, biodistribution of Photofrin® into Sprague Dawley rat has been investigated by
methodology for radiolabelleing of Photofrin® with
labelling efficiency of Photofrin® with
99m
Tc. In addition, it was explored that
99m
Tc is more than 95%. The current technique is
simpler and efficient as compared to the earlier published protocol. In the second part of this
experimental study, different photosensitizer‟s uptake was explored in the in vitro model e.g.
different cell lines (HepG2, RD, Hep2C, AG1518 and FM55P). Study of optimal dose of
laser, cellular totoxicity and phototoxicity were also the part of our experiment. The third
aspect of study relates to in vivo study, normal rat liver were treated as biological sample,
PDT under illumination of different wavelengths of light (630 nm, 660 nm, 600 nm and its
alternate combinations) has been performed and proved that effectiveness of 630 nm of
wavelength is more efficient for depth of necrosis as compare to other wavelengths of light
source. Finally, the synergistic effect of toxicity of zinc oxide nanorods (ZnO NRs)
conjugated with 5-ALA, Photofrin® and PPDME was determined for the treatment of
localized cancer cells. Cell toxicity due to microinjection and free standing drug delivery was
observed by detection of reactive oxygen species (ROS) liberation, and verified by MTT
assay. It is successfully demonstrated that UV-A irradiation increased toxicity and caused
significant production of ROS which leads to cell necrosis within few minutes. Zinc oxide
nanorods are toxic for both normal as well as malignant cells under exposure of ultraviolet
(UV) containing 240 nm of wavelength.