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Reactive oxygen species (ROS) are molecules produced in living organisms, in the environment, and in various chemical reactions. The main species include, among others, singlet oxygen (1O2), the superoxide anion radical (•O2−), the hydroxyl radical (HO•), and the hydroperoxyl radical (HOO•). In general, the reactivity of 1O2 is lower than that of HO• but even higher than that of •O2−. Singlet oxygen is the lowest energy excited state of molecular oxygen, but it is also a highly reactive species, which can initiate oxidation reactions of biomolecules such as amino acids, proteins, nucleic acids, and lipids, either by a direct reaction or by the induction of ROS. Singlet oxygen is a highly reactive electrophilic species that reacts with electron-rich molecules and is related to several types of pathologies. To inhibit the oxidation of biomolecules with this species, some substances act as antioxidants by performing a quenching effect. In this chapter, aspects such as its physicochemical properties, methods of generation and detection, as well as the reactivity of this molecule are detailed.
Hospital Clínico Universitario, Avenida de Ramón y Cajal, Valladolid, Spain
José Manuel Pérez de la Lastra*
Institute of Natural Products and Agrobiology, CSIC-Spanish Research Council, La Laguna, Spain
Celia Andrés Juan
Cinquima Institute and Department of Organic Chemistry, Faculty of Sciences, Valladolid University, Valladolid, Spain
Francisco J. Plou
Institute of Catalysis and Petrochemistry, CSIC-Spanish Research Council, Madrid, Spain
Eduardo Pérez-Lebeña
Sistemas de Biotecnología y Recursos Naturales, Valladolid, Spain
*Address all correspondence to: jm.perezdelalastra@csic.es
1. Introduction: Singlet oxygen (1O21Δg or 1O2*)
Oxygen is the most abundant element in the earth’s crust, mainly in its gaseous biatomic molecule form, constituting 21% by volume of dry air. It is one of the most biologically important elements because of the type and number of reactions in which it participates, providing the thermodynamic force necessary for the metabolism of all higher organisms. Molecular oxygen in its basal state has an open-shell electronic configuration, with two electrons of equal spin occupying different degenerate molecular orbital. It is only capable of accepting one electron at a time during a redox (radical-type) reaction, reacting slowly with most organic molecules. It has two excited states of singlet multiplicity. The lower energy state is designated as O2(1Δg) or 1O2, and the electron distribution in 1Δg has antiparallel spins, the two electrons occupy the same orbital with opposite spins, therefore the spin restriction does not exist and it is able to accept two electrons at a time, thus increasing its oxidative capacity compared to 3O2. The next excited singlet level is represented by the symbol O2(1Σg+), Figure 1.
Figure 1.
Electronic configuration molecular oxygen and the first two states mentioned.
Because of the high energy, low stability, and shorter lifetimes of the O2 state (1Σg+), the term “singlet oxygen” commonly refers to the 1O2 state. Singlet oxygen, or the first excited state of oxygen, is a highly oxidizing species that is generated by a light-activated compound, called a photosensitizer, and appears to play a significant role in solution reactions. It is found at 22.5 Kcal/mol above the basal state. This species emits phosphorescent light in the infrared region (1270 nm). The higher energy state (1Sg+), on the other hand, is rapidly deactivated at 1Dg and therefore will not be as reactive. The two energetically closest electronically excited states are singlet states, whose spectroscopic notations are 1Δg and 1Δg+. Singlet oxygen (1O2) is an electronically excited species of molecular oxygen (O2) and participates in numerous oxidation reactions as an activated species and plays a key role in many biological processes, Figure 2.
Figure 2.
Energy diagram for O2. The singlet states of oxygen are 156.9 and 94.2 kJ/mol higher in energy than its ground triplet state.
The transition between the triplet ground state (3Σg−) and the first excited singlet (1Δg) is spin, symmetry, and parity forbidden; therefore, direct excitation of the ground state to form singlet oxygen is very unlikely, and gas-phase singlet oxygen has an extremely long lifetime (72 min) [1]; however, interaction with solvents reduces the lifetime, depending on the solvent and varies from 10−3 to 10−6 s [2], with the shortest lifetime observed in water [1].
From the values in Table 1, it can be concluded that some of the solvent characteristics that influence the lifetime are the number of C-H and O-H bonds and the presence of halogen and deuterium atoms [2].
Because 1O2 is a molecule in an electronically excited state, it is very unstable with respect to its ground state, and once generated it can undergo various spontaneous processes to deactivate it. Such deactivation can occur by different routes, Figure 3.
Figure 3.
Singlet oxygen deactivation pathways. The molecule that interacts with O2(1Δg) is commonly called quencher (Q).
The non-radiative deactivation process of 1O2 (kd) involves the transfer of electronic energy to the vibrational levels of the solvent. The radioactive deactivation process of 1O2 (kdr) occurs when 1O2 decays to its ground state emitting phosphorescent radiation of 1270 nm. The value of this rate constant depends on the medium.
The deactivation processes by molecules in the medium can be either physical (kq) or chemical (kr). Physical deactivation of 1O2 occurs mainly by energy transfer mechanisms. Molecules with several conjugated double bonds, such as long-chain polyenes, quinones, dyes, and transition metal complexes, are some examples where this type of deactivation occurs [3].
The reactive deactivation of singlet oxygen, as the name suggests, refers to its chemical reaction with a wide variety of organic molecules. Singlet oxygen is a highly reactive electrophilic species and has the ability to rapidly attack organic compounds. It is about 1000 times more reactive than the basal state of oxygen. This high reactivity is simply because many of the substances with which it reacts are in the singlet basal state, so the reaction is a singlet-singlet reaction, more likely than a triplet-singlet reaction, as it should be with oxygen in its basal state. As singlet molecular oxygen possesses a pair of electrons with opposite spins in the highest occupied molecular orbital, they give O2(1Δg) dienophilic properties, which explains its significant reactivity towards electron-rich organic molecules, particularly those with conjugated double bonds [4]. These reactions are electrophilic [4π + 2π], [2π + 2π], and ene-type additions, leading to the formation of allylic hydroperoxides, dioxetanes, or endoperoxides [5, 6, 7, 8].
Singlet oxygen also oxidizes sulfur, selenium, phosphorus, and nitrogen compounds, Figure 4. Singlet oxygen-mediated oxidation reactions have been explored with a variety of organic molecules containing heteroatoms.
Figure 4.
Singlet oxygen-mediated photooxidations: (a) cycloaddition [2 + 2], (b) [4 + 2] cyclo addition, (c) 1,3-ene addition, and hetero atom oxidation. In all these reactions the primary products formed can undergo rearrangements to give a wide range of stable oxidized products.
There are three main sources for generating singlet oxygen: photochemical, chemical, and in vivo reactions, Figure 5.
Figure 5.
Sources of singlet oxygen.
3.1 Chemical generation
There are many chemical reactions, one of the best-known examples being the reaction of NaClO with H2O2. The decomposition reaction of H2O2 in the presence of sodium hypochlorite or sodium hypobromite is the oldest reaction [9] for the formation of singlet oxygen, Figure 6.
Figure 6.
Singlet oxygen generation from H2O2 by NaOCl.
1O2 is formed from the chlorine peroxide anion (ClOO−), which is an intermediate in the above reaction. The best results are achieved when H2O2 decomposition is performed using a MoO42− catalyst [10, 11, 12, 13], Figure 7.
Figure 7.
Singlet oxygen generation from H2O2 by the [MoO4]2− catalyst.
Among the inorganic peroxides, calcium peroxide diperoxohydrate (CaO2-2H2O2), which is easily prepared by treating CaCl2 or Ca(OH)2 with H2O2 is of special interest for its ability to release 1O2. In the first step, Ca(OH)2 is converted into CaO2-8H2O, which takes up two H2O2 molecules giving CaO2-2H2O2. By thermolysis at moderate temperature, the latter peroxide decomposes into 1O2 and CaO2-8H2O. This catalytic cycle would operate until complete disproportionation of H2O2 and leave CaO2-8H2O as the final product [14], Figure 8.
Figure 8.
Singlet oxygen generation from CaO2-2H2O2.
Singlet oxygen can also be generated chemically by the decomposition of ozonides of triphenylphosphite [15], Figure 9.
Figure 9.
Singlet oxygen generation from ozonides of tri-phenyl-phosphites.
1O2 production from acyl peroxides such as benzoyl peroxide and lauryl peroxide [16, 17], Figure 10.
Figure 10.
Singlet oxygen generation from benzoyl peroxide.
By decomposition of aromatic endoperoxides, singlet oxygen is also generated chemically. Certain dienes (anthracenes, naphthalenes, and pyridones) react with O2(3Σg-) via sensitized photooxygenation to produce endoperoxides, which by heating dissociate and regenerate the starting hydrocarbon and 1O2. The thermal stability of endoperoxides depends on the structure of the aromatic or heteroaromatic hydrocarbon. These organic endoperoxides are called reversible molecular singlet oxygen transporters. The lifetime of the endoperoxide precursors depends on the temperature and chemical structure of the dienes. Derivatives of naphthalenes, anthracenes, and pyridones are among the most studied examples that can undergo reversible endoperoxide formation for this purpose, Figure 11. All carriers are based on the reversible [4 + 2] cycloaddition of 1O2 to a diene and are therefore generated by photooxygenation.
Figure 11.
Generation of singlet oxygen based on the formation and decomposition of endoperoxides.
3.2 Photochemical generation
The absorption of light by a photosensitizer in its ground state (1Sens) transforms it into an excited singlet state (1Sens*). This short-lived state is rapidly converted through intersystem crossover into a more stable and longer-lived species, the excited triplet state (3Sens*). The photosensitizer in its triple-excited state has the ability to transfer its energy to the 3O2 dissolved in the medium. As a consequence of this transfer, the sensitizer is regenerated in its basal state, and the O2 remains in its singlet excited state, Figure 12.
Figure 12.
The most widely used method in the generation of O2(1Δg) is photosensitization.
Photosensitization represents the most convenient, safe, easy, and environmentally friendly method for 1O2 generation. The generation of singlet oxygen through photosensitization has been widely exploited in photodynamic therapy, environmental remediation, and synthesis [18].
3.3 Possible production of singlet oxygen in vivo
Some of the possible biological sources of 1O2 generation are shown in Figure 13.
Figure 13.
Generation of singlet oxygen in biological systems.
Possible biological sources of O2(1Δg) include (i) reactions catalyzed by peroxidases (myeloperoxidase) or oxygenases (lipoxygenases) [19, 20], (ii) recombination of peroxyl radicals can lead to the release of 1O2 as a result of the decomposition of transient tetroxides according to Russell’s concerted mechanism (Russell reaction) [6, 21], (iii) oxidation with ozone of amino acids, peptides, and proteins, (iv) hydrogen peroxide reactions with hypochlorite or peroxynitrite, (v) ozone oxidation of amino acids, peptides, and proteins [22], (vi) hydrogen peroxide reactions with hypochlorite or peroxynitrite [23, 24], (vii) thermolysis of endoperoxides [25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35], (vii) in vitro photodynamic processes involving type-II photosensitization reactions using suitable dyes [36, 37, 38], and (viii) UV irradiation of aromatic amino acids in proteins and immunoglobulins.
1O2 has been gaining much attention due to its pivotal role in a wide variety of chemical and biological processes, for example, plant signaling, organic synthesis, oxidation of food and beverages, or photodynamic therapy [39, 40], Figure 14.
Figure 14.
The following sections outline different applications that have been developed over the last decades.
4.1 Photodynamic therapy (PDT)
Photodynamic therapy (PDT) has received increasing attention for the treatment of cancer and other diseased tissues as this methodology allows noninvasive, selective, and localized destruction of tumor cells with reduced side effects. PDT consists of the administration of a photosensitizer, which is selectively accumulated in certain cells or tissues so that with subsequent irradiation and in the presence of oxygen, it triggers photooxidation of biological materials and subsequent cell death.
PDT is composed of three components, Figure 15. Each of these components alone lacks curative properties. The contribution of each depends on the type and dose of PS, the time between administration and exposure to light, the intensity of light, and the concentration of oxygen generated.
Figure 15.
PDT components.
PDT combines light, molecular oxygen, and a photosensitizer (PS) for the production of reactive oxygen species (ROS) such as singlet oxygen (1O2) and free radicals that induce oxidative stress and eventually cell death. PDT was the first example of a drug-device combination approved by the Food and Drug Administration (FDA) for the production of reactive oxygen species (ROS) such as singlet oxygen (1O2) and free radicals that induce oxidative stress and eventually cell death [41]. PDT was the first example of a drug-device combination approved by the Food and Drug Administration (FDA) [42].
4.2 Light sources
Most Ps are activated with red light between 630 and 700 nm, which has a tissue penetrating power between 0.5 cm (at 630 nm) and 1.5 cm (at 700 nm) [43]. Lasers and light-emitting diodes (LEDs) coupled to flexible fiber optic devices are used as light sources. Depending on the depth of the pathologies to be treated, LEDs can be implanted at the end of different catheters to form screens for irradiation of large areas. The wavelength required will be determined by the PS with which it is to be associated and applied in the most focal way possible on the tissue to be treated. However, the most commonly used light sources in photodynamic treatments are lasers.
4.3 Photosensitizing agent in photodynamic therapy
A PS is defined as a compound capable of absorbing light and subsequently triggering a photophysical or photochemical reaction in response to it. For clinical use, it must meet a number of characteristics as summarized in Figure 16 [39, 44].
Figure 16.
PS properties.
The PS most suitable for PDT can be divided into two main groups: porphyrinoid or non-porphyrinoid derivatives [44, 45, 46, 47], Figure 17. Porphyrinoid-based derivatives are the most widely used in PDT applications as their extended π-systems confer unique photochemical characteristics that are valuable for their use as photosensitizers [48]. Within the porphyrinoid PS, they are usually classified into first-, second-, and third-generation photosensitizers depending on their evolution [49]. Natural porphyrins and their derivatives constitute the first generation of PS. Most of the PS under investigation for the treatment of cancer and other diseases is based on the tetrapyrrole core that includes porphyrins, chlorins, bacterio-chlorins, phthalocyanines, and texaphyrins. These molecules have been chosen for their low toxicity in the absence of light to mammalian and animal cells and for their tumor-localizing properties. PS that have been studied for their ability to kill microorganisms are halogenated xanthenes such as rose bengal (RB), chlorinated poly-L-lysine-chlorinacorinate, and phenothiazines such as toluidine blue O (TBO) and methylene blue [50] and poly-L-lysine-chlorinate conjugates [51].
Figure 17.
Types of photosensitizers.
4.4 First-generation photosensitizers
First-generation PSs are a complex mixture of compounds among which hematoporphyrin (HpD) and photofrin (R) derivatives are the representatives of the first-generation Fs. Photofrin is one of the few photosensitizers approved for the treatment of early and advanced esophageal and lung cancer by the US FDA and by various health agencies worldwide. It is now being extended to the therapy of different oncological pathologies of the head, neck, abdomen, thorax, brain, bowel, cervical, skin, and breast Photofrin® (as HPD) causes persistent photosensitization of the skin. This required avoidance of intense sunlight for at least 30 days after drug administration. HpDs are a complex mixture of monomers, dimers, and oligomers, linked together by the formation of ethers, esters, and carbon-carbon bonds [44], Figure 18.
Figure 18.
First-generation porphyrin derivatives.
4.5 Second-generation photosensitizers
Second-generation photosensitizers have been developed since the late 1980s. They are pure compounds of known chemical structure with absorption maxima at wavelengths above 630 nm, high molar extinction coefficients, quantitative 1O2 formation, and a reduction in the side effects and undesirable properties of the first generation. The major disadvantage of these is that they are highly lipophilic, which hinders their bioavailability, favors self-aggregation, and poses a challenge for the development of a pharmaceutical form for intravenous administration.
4.5.1 Porphyrin photosensitizers
Porphyrin derivatives such as meta-tetra-(hydroxyphenyl)-porphyrin (m-THPP, Foscan, or Temoporphyrin) and 5,10,15,20-tetrakis(4-sulfonatophenyl)-21H-23H-porphyrin (TPPS4). These compounds are pure, extremely potent structures, which are photoactivated at wavelengths longer than those corresponding to HpD, with higher molar extinction coefficients. This group also includes macrocyclic porphyrin derivatives such as chlorines, bacterio-chlorines, phthalocyanines, porphyrins, and texaphyrins. Due to the potency of the second-generation Fs, the drug doses and light intensity required to obtain a photofrin(R)-like response are up to 100 times lower, Figure 19.
Figure 19.
(a) Second-generation porphyrin derivatives and (b) Second-generation porphyrin macrocycles.
4.5.2 Non-porphyrin photosensitizers
The development of non-porphyrin PSs, Figure 20, for application in photodynamic therapy lags considerably behind the evolution of porphyrin derivatives. Cationic compounds, such as phenothiazines, have high molar extinction coefficients between 600 and 800 nm, including methylene blue and toluidine blue. Methylene blue has been applied in the clinical treatment of basal cell carcinoma and Kaposi’s sarcoma. In addition, there are in vitro assays of adenocarcinoma, bladder carcinoma, and cervical tumor cells. Toluidine blue has been extensively studied for the inactivation of various pathogenic microorganisms. Both thiazine derivatives are currently being evaluated for the treatment of chronic periodontitis. Literature has shown that the mitochondrial membrane potential of tumor cells is more negative than that of normal cells so that cationic PSs are retained mainly in the cells to be treated. The bacterial cell wall has anionic components that readily interact with cationic drugs.
Figure 20.
Chemical structure of non-porphyrin photosensitizers.
Rose bengal has shown good results in the photodynamic treatment of breast carcinoma and metastatic melanoma. 4,5-dibromorhodamine methyl ester is effective against graft-versus-host disease, resulting in the destruction of lymphocytes by apoptosis.
Hypericin is a natural anthraquinone with defined photochemical properties and shows selectivity for tumor cells. Merocyanin 540 is the representative of the cyanins used in the treatment of leukemia and neuroblastoma.
4.5.3 Endogenous photosensitizer: precursors
Protoporphyrin IX (PpIX) is an endogenous photosensitizer. Under normal conditions, PpIX is present at an extremely low concentration to produce a photosensitizing reaction. To stimulate the synthesis of protoporphyrin IX, it is necessary to administer an excess of amino levulinic acid (ALA) and its derivatives, ALA-methyl ester (MAL) and ALA hexyl ester (HAL), thus stimulating the synthesis of PpIX, which can accumulate in damaged tissue and be applied in the photodynamic treatment of different pathologies. It has been used in the treatment of actinic keratosis, carcinoma, basal cell carcinoma, Bowen’s disease, and bladder cancer. PDT with ALA and its derivatives, ALA-methyl ester (MAL) and ALAhexyl ester (HAL), is an approved treatment for a number of malignant and premalignant conditions (Figure 21).
Figure 21.
Chemical structure of Protoporphyrin IX and of ALA MAL and HAL.
4.6 Third-generation photosensitizers
Third-generation photosensitizers are called nano photosensitizers and are made up of a combination of PSs and different vector systems. They are proposed as a solution to overcome the problems of low water solubility of the first- and second-generation Ps as most of them have an aromatic character.
Numerous delivery strategies have been evaluated with the aim of achieving a highly selective and effective therapy. Among the drug carrier systems used in the development of third-generation PSs, applicable in PDT are polymeric nanoparticles, solid lipid nanoparticles, nanostructured lipid carriers, gold nanoparticles, hydrogels, liposomes, liquid crystals, dendrimers, and cyclodextrin.
4.6.1 Liposomes
One of the most recent and successful applications of liposomes is to serve as delivery vehicles for photodynamic agents to improve their solubility, specificity, bioavailability, and tendency to aggregate. Therefore, liposomal photosensitizers as third-generation formulations have shown great potential to increase the efficacy of photodynamic cancer therapy and consist of concentric vesicles formed by one or more concentric natural or synthetic phospholipid bilayers enclosing an aqueous compartment. Nontoxic, highly biocompatible, and biodegradable, these delivery systems have allowed increasing the activity of Ps in vitro and in vivo, reducing their toxicity and improving their biodistribution [52].
4.6.2 Micelles
Micelles are monolayer structures formed by amphiphilic surfactants, also called amphipathic surfactants, which are molecules that have one hydrophilic end, that is they are soluble in water, and one hydrophobic end, which means that they repel water.
Polymeric micelles have been widely used in recent years due to their higher stability compared to micellar systems based on conventional surfactants. They are prepared by association of copolymers dispersed in an aqueous medium, forming particles with diameters of less than 100 nm [53]. Polymeric micelles are presented as an alternative for the delivery of hydrophobic Ps and have the following advantages (i) simple preparation, (ii) efficient drug loading without chemical modification, (iii) controlled release [54], and (iv) no side effects of skin photosensitivity [55].
4.6.3 Solid nanoparticles
Solid nanoparticles are a promising new tool for drug delivery in PDT [56, 57]. The advantages over second-generation Ps can be summarized as (i) ability to deliver a large amount of drug to target cells, (ii) prevent degradation in the biological environment, (iii) incorporate multiple components as contrast agents, and (iv) incorporate of different ligands in order to increase selectivity [58].
The solid nanoparticles, most commonly used in the development of third-generation Ps, are polymeric, silica, and gold nanoparticles [57, 59]. Silica nanoparticles have numerous advantages over polymeric systems such as their nontoxic nature, inert, and stable properties. As they are nonbiodegradable, particle size control is necessary to ensure their elimination from the body via the kidney and to avoid their uptake by the reticuloendothelial system. Due to their high porosity, silica nanoparticles have a high PS loading capacity and contribute significantly to the efficacy of PDT.
Gold nanoparticles increase the field of incident light around them, which could increase the excitation efficiency of the PS they carry [60]. The vehiculization of porphyrins, phthalocyanines, and thiazines on gold nanoparticles increased (i) blood circulation time, (ii) selective delivery to tumor tissues, (iii) 1O2 generation yield, and (iv) photodynamic activity of free PSs [61].
Most PS in their ground state has two electrons with opposite spins. Light absorption leads to the transfer of an electron to a higher energy orbital. This excited PS is very unstable and emits this excess energy in the form of fluorescence and/or heat. Another possibility is that an excited PS can undergo cross-system crossover to form a triplet state. The photosensitizer in the triplet state can decay without radiation to the ground state or transfer its energy to molecular oxygen. This step leads to the formation of singlet oxygen, and the reaction is called a type-II process [62]. A type-I process can also occur [63], Figure 22.
Figure 22.
Dynamic singlet oxygen therapy: Sensitizer diagram.
In the type-I process, electron transfer occurs between the activated PS and the surrounding molecules leading to the release of free radicals. These radicals are highly active and interact with oxygen-producing endogenous molecules to produce anion superoxide, hydroxyl radical, hydrogen peroxide, and free radicals. These ROS cause damage to the integrity of cell membranes and their internal structures.
The type-II process, this is the interaction of PS with oxygen. For this reaction to take place, PS must be in its triplet form, activating oxygen to its active or singlet form (1O2), which allows it to interact with a large number of substances directly such as amino acids or lipids. The short half-life of this singlet oxygen (<0.4 milliseconds) means that its diffusion range is limited to 45 nm in the cellular medium, and destruction is only limited to the intracellular structures, it can access [64, 65].
PDT is a minimally invasive outpatient therapeutic modality that has low toxicity and can be applied repeatedly at the site of action. In oncology, it can be combined with chemotherapy, ionizing radiation, or surgery. PDT is an approved technique for the treatment of some types of cancer and for antimicrobial therapies.
6.1 Photodynamic therapy of cancer
Photosensitizers (PS) can be used in various types of tumors. PS has been used as therapeutic agent for more than a century. The clinical use of eosin in the treatment of skin cancer can be given as an example of the first applications of PDT. The first objective was to treat skin tumors by using topical eosin [66, 67].
According to the World Health Organization (WHO), cancer is a group of cellular diseases characterized by unregulated cell growth. In the early stages, it is localized in healthy tissues and spreads to neighboring tissues or even to other organs of the body through metastatic cells. The idea of using photodynamic therapy (PDT) as a new treatment strategy was suggested in the early twentieth century. PDT has fewer side effects and toxicity than chemotherapy and/or radiotherapy. PDT is a particularly attractive alternative to conventional antitumor drugs due to its fundamental specificity and selectivity. This excitation causes the photosensitizer to generate singlet oxygen and other reactive oxygen species. PDT has been used in several types of cancer, including non-melanoma skin cancer, bladder cancer, esophageal cancer, head and neck cancer, and non-small cell lung cancer (NSCLC), Figure 23.
Figure 23.
PDT antitumor treatments.
The PDT clinical procedure involves four stages, as shown in Figure 24.
Ps is administered to the patient, usually topically or intravenously.
Between 3- and 96-hours elapse before the affected area is illuminated. During this time, the drug is distributed throughout the body and selectively localized in the affected cells.
The affected area is irradiated locally using an appropriate irradiation source for photodynamic treatment.
A series of intracellular reactions are triggered, which give rise to the formation of ROS that produce irreversible biological damage in the treated area, leading to cell death. Cell destruction can be triggered by different pathways [44, 68].
Figure 24.
Representation of an antitumor treatment with PDT.
6.2 Non-oncological applications of PDT
PDT has been mainly focused on cancer treatment, but in recent years, new applications in different fields are being evaluated, Figure 25.
Figure 25.
Non-oncological applications of PDT.
Esthetics: Photo depilation is based on using a laser that irradiates at an appropriate wavelength (depending on the color of the hair and the color of the skin) to permanently remove the hair. The action of topically applied ALA is currently being studied to improve the photo-depilation technique.
Dermatology: PDT is used to treat non-oncological dermatological diseases such as psoriasis, vascular malformations, and acne [69, 70, 71].
Inactivation of bacteria: The increasing resistance of bacteria to antibiotics has led to the development of alternative antimicrobial techniques. Certain bacteria can be inactivated by being illuminated after an incubation period with certain porphyrins and phthalocyanines. This new application may be of great use in the treatment of internal cavity cleaning and in the treatment of oral conditions.
Virus inactivation: Photoinactivation of viruses in human blood as a method to sterilize blood and blood products for transfusion [72].
Ophthalmology: Age-related macular degeneration (AMD) is a leading cause of blindness and is due to the rapid abnormal growth of blood vessels in the retina. The results obtained by treating this disease with PDT show a hopeful future.
Arteriosclerosis: The possibility of treating this disease with PDT is based on the fact that atheroma plaques in damaged arteries retain higher concentrations of porphyrins than the normal vascular wall [69].
Gynecology: PDT is an alternative to hysterectomy for women with dysfunctional uterine bleeding [73, 74].
This research was funded by Agencia Canaria de Investigación, Innovación y Sociedad de la Información (ACIISI) del Gobierno de Canarias, Project ProID2020010134, Caja Canarias, Project 2019SP43, the Spanish Ministry of Economy and Competitiveness (Grant PID2019-105838RB-C31) and the State Plan for Scientific, Technical Research and Innovation 2021–2023 from the Spanish Ministry of Science and Innovation (project PLEC2022-009507) and the State Plan for Scientific, Technical Research and Innovation 2021–2023 from the Spanish Ministry of Science and Innovation (project PLEC2022-009507).
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Written By
Celia María Curieses Andrés, José Manuel Pérez de la Lastra, Celia Andrés Juan, Francisco J. Plou and Eduardo Pérez-Lebeña
Submitted: 04 May 2023Reviewed: 31 May 2023Published: 22 October 2023
Open access peer-reviewed chapter
