# Natural Photosensitizers in Clinical Trials
## 3 Natural Photosensitizers in Clinical Trials
### Anthraquinones  
Anthraquinones are obtained from plant elements in the _Rubiaceae_ group. Several studies have been reported in the literature in which such compounds were used as photosensizers. ROS generated during PDT with the photosensitizer in question cause severe oxidative damage inside the cell, leading to various forms of cell death, such as apoptosis, necrosis, or autophagy, depending on the intensity of the treatment and the type of anthraquinone. Some anthraquinones can additionally inhibit the defense mechanisms of tumor cells, leading to the accumulation of ROS and increasing the efficacy of PDT [75]. One study involved the treatment of cancer cells of a breast cancer line that was largely cured [76; 77]. When exposed to light, these compounds were able to effectively destroy or severely damage cancer cells. The photosensitizing efficacy of anthraquinones was evident at a concentration of 100 uM and a light dose of 1 J/cm\({}^{2}\). These results suggest that anthraquinones had a strong effect on cancer cells under clearly defined concentration and irradiation conditions. The mechanism of cell elimination by light-activated anthraquinones is related to the production of singlet oxygen, a reactive form of oxygen capable of damaging cells and their components, leading to cell death [77]. The value of these findings suggests the potential use of anthraquinones as a promising phototoxic agent for anticancer therapy, particularly for breast cancer. However, before such a therapy can be used in clinical practice, further thorough research and clinical trials are needed to confirm its efficacy and safety [78]. The anthraquinone being clinically tested as a photosensitizer in PDT is emodin. It is a natural anthraquinone derivative that is found in many commonly used Chinese medicinal herbs, such as _Rheum palmatum_, _Polygonum cuspidatum_, and _Polygonum multiform_[79]. It is recognized as a tyrosine kinase inhibitor and anticancer drug, active against various cancer cells, including lung, breast, liver, and ovarian cancer cells [80]. Previous studies have shown its potential as a photosensitizer used in anticancer therapy for skin cancer [81]. Anthraquinones in Clinical Trials of Photodynamic Therapy  
We located one clinical trial using emodin as a photosensitizer. [PERSON] et al. studied PDT with nano-emodin in donor site wound healing after free gingival transplantation (Figure 3). The therapeutic regimen consisted of applying n-Emo gel with emodin to the wound surface for five minutes, followed by irradiation with a light-emitting diode with a wavelength of 450 \(\pm\) 10 nm, an output intensity of 1000 \(\pm\) 1400 mW/cm\({}^{2}\), and an energy density of 60-80 J/cm\({}^{2}\) for one minute. The LED was positioned perpendicular to the wound surface at a distance of 1 mm. Their work showed that this strategy can act as an adjunct to conventional wound care in the treatment of postoperative complications at the donor site after free gingival graft surgery [82]. Characteristic of clinical work investigating photodynamic therapy with natural photosensizers are presented in Table 2.