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142    CHAPTER 6  Laser-assisted cancer treatment




                            In addition to the tendency to be absorbed in NIR region and nontoxicity in the
                         absence of NIR irradiation, photosensitizer must successfully be accumulated in the
                         desired side and also it should be able to induce cell death via activating of dendritic
                         and T cells. In the following section, some photosensitizers making the above criteria
                         will be described.


                         6.3.1  Methylene blue
                         Methylene blue (MB) is one of the organic dyes being able to kill malignant cells.
                         Owing to its positive charged and low molecular weight, the interaction of MB with
                         mammalian cells increased lead to be chosen as a suitable candidate for PDT applica-
                         tion. Although MB commonly applied in antimicrobial PDT, there have been several
                         studies focusing on the application of MB in PDT due to its cost-effectivity and
                         availability. Samy et al. utilized MB for PDT to study the outcomes on basal cell
                         carcinoma in clinical stage. Complete treatment with good cosmetic outcomes was
                         observed in 11 out of 17 patients [41]. Currently, the application of MB is limited
                         due to the lack of stability after intravenous administration leading to the reduction of
                         leuco MB with no photosensitizing properties [42]. Encapsulation of MB in nanopar-
                         ticles to maintain their activity during blood circulation can be a solution.


                         6.3.2  Photogem
                         Photogem is originated from hematoporphyrin being one of the first generations
                         of the photosensitizers with photochemical properties similar to Photofrin. Photo-
                         gem got approved for clinical usage from “Brazilian Health Surveillance Agency
                         (ANVISA)” and “Pharmacology State Committee of the Russian Federation”. The
                         maximum absorption of Photogem is between 500 and 630 nm. Its main side effect is
                         related to the long-lasting photosensitivity in the body after several weeks of admin-
                         istration decreased by incorporating it into the drug delivery system. Low absorption
                         spectra of the Photogem in the therapeutic window and long-lasting photosensitiv-
                         ity led to introduce the second generation of photosensitizes including chlorins and
                         5-aminolevulinic acid [43].


                         6.3.3  Chlorins
                         Chlorins with strong light absorption in the therapeutic window mainly between 640
                         and 700 nm have absorbed great attention due to its natural origin. Being hydrophilic
                         reduced types of porphyrins, chlorins structure is similar to porphyrins. One of the
                         most studies chlorin used as a photosensitizer is mono-l-aspartyl chlorin e6 which
                         has two significant features including strong absorption between 650 and 680 nm and
                         a high yield of free radical production. Another promising photosensitizer belonged
                         to chlorin family is Photodithazine. It is one of the second generations of the pho-
                         tosensitizing agent with little skin photosensitivity [44]. Chlorins have been widely
                         used for oral cancer treatment [45]. In 2010, Parihar et al. investigated the effect
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