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Molecules 2020, 25, 4102 6 of 22 Molecules 2020, 25, x FOR PEER REVIEW 7 of 22 3. PDT’s Cancer Cell Death Mechanism PDT’s cancer cell death mechanism starts after the activation of administrated PS by a specific 3. PDT’s Cancer Cell Death Mechanism wavelength of light. The PS’s hydrophilic, hydrophobic, and ionic charge-related interaction nature PDT’s cancer cell death mechanism starts after the activation of administrated PS by a specific plays an important role in the targeting of particular cancer cell receptor (globulins and Low-Density wavelength of light. The PS’s hydrophilic, hydrophobic, and ionic charge-related interaction nature Lipoprotein (LDL) receptors) [34]. After the activation of PSs, the cancer cell death mechanism plays an important role in the targeting of particular cancer cell receptor (globulins and Low-Density might occur in three main pathways (Figure 1), namely, apoptosis, necrosis, and autophagy [33,65,66]. Lipoprotein (LDL) receptors) [34]. After the activation of PSs, the cancer cell death mechanism might However, the level of cell death induced by PDT may be affected by various aspects, including occur in three main pathways (Figure 1), namely, apoptosis, necrosis, and autophagy [33,65,66]. subcellular localisation, bioavailability, the physicochemical nature of the PS, the cellular oxygen However, the level of cell death induced by PDT may be affected by various aspects, including concentration, as well as the applied light intensity and wavelength [67]. In general, the light-absorbed subcellular localisation, bioavailability, the physicochemical nature of the PS, the cellular oxygen PS interacts with cellular oxygen and highly produce ROS (hydroperoxides, superoxide, or hydroxyl concentration, as well as the applied light intensity and wavelength [67]. In general, the light- 1 abhoyvder-omxyenltriaodniecadlsm)aeschwaenlilsamsss.inBgoltehttoyxpyege1nan(1dO2).rTeahcetsieonpsromdauyceodccRuOrSsecpanariantdeluyceorcainceormoubsincaeltlion, budtetaytphev1ia(gtheenearbaotvioen-moefnRtOioSnefdolmloewcehdanbiysmthse. Baoptohpttyoptiec1cealnlde2artehamctieocnhsamniasymo)ciscucrosmepmaornatleylyexohriibnited bycomobsitnaptiporno,vbeudtPtySpse[617](.generation of ROS followed by the apoptotic cell death mechanism) is commonly exhibited by most approved PSs [67]. 4. PS from Natural Resources The effectiveness of PDT is mainly based on the PS; it should possess all the properties of the PS as The effectiveness of PDT is mainly based on the PS; it should possess all the properties of the PS raadbicsaolrsb)eadsPwSeilnltaesrascitnsgwleithoxceylgluelnar(oOxy)g.eTnhaensdehpirgohdluycperdodRuOcSeRcaOnSi(nhdyudcreopcaenrocxeirdoeuss,scuelpledroeaxtidhev,ioarthe 2 4. PS from Natural Resources previously explained. The PS can be divided into first- and second-generation types. Hematoporphyrin ®® as previously explained. The PS can be divided into first- and second-generation types. and its derivative Photofrin were classified as first-generation PSs. After extensive studies, new and ®® Hematoporphyrin and its derivative Photofrin ®®were class®ifi®ed as first-generation PSs. After improved second-generation PSs, such as Levulan , Alasens , and Foscan have been introduced extensive studies, new and improved second-generation PSs, such as Levulan®®, Alasens®®, and for PDT application (Table 1). Although these are widely used for various cancer treatments, their Foscan have been introduced for PDT application (Table 1). Although these are widely used for clinical usage is limited by various drawbacks such as lack of chemical purity, a longer half-life, various cancer treatments, their clinical usage is limited by various drawbacks such as lack of accumulation in tissues and poor ability in relation to depth of tissue penetration [31–39]. chemical purity, a longer half-life, accumulation in tissues and poor ability in relation to depth of Subsequently, there are some research reports on PSs with potent pharmaceutical properties tissue penetration [31–39]. to overcome the shortcomings of first- (Porphyrin based sensitisers) and second-generation Subsequently, there are some research reports on PSs with potent pharmaceutical properties to (non-porphyrin derivatives) PSs [35–37]. These drawbacks of current PSs specifically imply the overcome the shortcomings of first- (Porphyrin based sensitisers) and second-generation (non- need for new PSs as anticancer agents from natural resources. The discovery of new PS compounds porphyrin derivatives) PSs [35–37]. These drawbacks of current PSs specifically imply the need for with anticipated pharmacological properties and clinical application is an inspiring task. Recently, new PSs as anticancer agents from natural resources. The discovery of new PS compounds with a greater number of plant-based compounds have been reported for their anticancer activity, and these anticipated pharmacological properties and clinical application is an inspiring task. Recently, a compounds are pharmaceutically very important for the development of potent drugs. The use of light greater number of plant-based compounds have been reported for their anticancer activity, and these to activate the bioactivities of natural products is generally called photopharmacology (a combination compounds are pharmaceutically very important for the development of potent drugs. The use of of photophysics and photochemistry). The absorption of lights (λ < 350 nm) by a molecule mainly light to activate the bioactivities of natural products is generally called photopharmacology (a decpoemnbdisnoatniotnheocfhprohmotophoyrseiccsoamnpdouphnodtoactthaecmheisdtr(yF)i.guTrhe2a)b[s3o6r,3p7ti]o. nThoifs lriegvhitesw(λprPDF Image | Role of Photoactive Phytocompounds in Photodynamic Therapy of Cancer
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