# Natural Photosensitizers in Clinical Trials
###### Abstract
In the excited state, it can transfer its energy to the oxygen molecule, which is normally in the triplet state (\({}^{3}\)O2). As a result of this interaction, oxygen passes to the singlet state (\({}^{1}\)O2), which is a highly reactive form of oxygen and can react with various biomolecules in the cell, leading to their damage. Singlet oxygen (\({}^{1}\)O2), which has not reacted with other compounds, returns to its more stable triplet (\({}^{3}\)O2) state over time [7]. Photodynamic therapy has a number of advantages over other forms of treatment. The specificity of its regimen and the activation of photosensizers depend on light, which allows the therapy to precisely target altered tissues while minimizing damage to healthy cells, which is the case, for example, in radiotherapy or chemotherapy [13]. Unlike other therapies, PDT also preserves fertility and does not affect pregnancy and childbirth [14]. Disadvantages of using PDT relative to other therapies primarily include the suboptimal properties of photosensizers, such as poor water solubility, limited depth of light penetration, and lack of good tumor-targeting efficiency. Other disadvantages of PDT include a complicated schedule, the need for multiple procedures, post-treatment patient follow-up, and problems with light hypersensitivity during the weeks following therapy [13]. In view of this, the search for new photosensizers is still ongoing [15]. In recent years, there has been a steady movement toward the use of natural substances and herbal medicines instead of synthetic chemotherapeutic drugs [16]. This direction is also evident in the search for new photosensizers [17]. Studies show that natural photosensizers isolated from plants or fungi are an alternative to the use of those of artificial origin [18; 19]. There are scientific reports indicating that natural photosensizers can be used to treat cancer and inflammatory, viral, or bacterial diseases, opening up the possibility of an even more effective form of photodynamic therapy [17]. Natural photosensizers have a number of advantages: low cytotoxicity, high selectivity, relatively greater safety than their synthetic counterparts, and easy availability [18; 20]. The use of natural photosensizers also faces difficulties, such as identification by the patient's immune system, rapid removal from the bloodstream, and limited accumulation in tumor tissue. To solve these problems, photosensizers are combined with natural cell membranes to form nanoparticles [21]. Another difficulty is that usually the detailed chemical composition of a given plant is not known, so a time-consuming and labor-intensive extraction process is required to isolate specific compounds precisely. Also important are the place of finding, climatic conditions, substrate composition, and many other conditions that affect the composition of individual plants, so that their properties in the photodynamic process will not be effective [22]. A number of natural compounds derived from plants tested for use as PSs have been established. Some of them have also been studied in the clinical setting. The current review focuses on presenting the results of clinical trials of natural-derived photosensizers. Since there have been many recent papers extensively summarizing the research on natural photosensizers [23; 24; 25], there is still a lack of papers accurately summarizing their clinical application; our work focuses on clinical trials. We also provide directions for future research for photosensizers of natural origin that have not yet been clinically tested.