# Natural Photosensitizers in Clinical Trials
## 4 Natural Photosensitizers Pending Clinical Trials
### Toliporphins  
Toliporphins are green tetrapyrrole pigments that are isolated from cyanobacteria [134]. Toliporphins localize mainly to the perinuclear region and primarily to the endoplasmic reticulum. The nuclear membrane damage observed after PDT with TPs can be attributed to either direct photosensitization by reactive oxygen species bound to the nuclear membrane or to the transfer of photo-oxidative damage from photoactivated TPs bound to the rough ER to the nuclear membrane, via inactivation of acyl-CoA:cholesterol-0-acyltransferase, a sensitive marker of ER membrane integrity [135; 136; 137]. The absorption maximum occurs at a wavelength of 660-680 nm. Its photosensitizing potential was tested with EMT-6 cancer cells in vitro and in vivo [135; 136]. TPs were tested in vivo in the treatment of subcutaneously injected EMT-6 tumor cells into mice with severe combined immunodeficiency. This PS was administered via the tail vein. One hour after administration of the photosensitizer, the tumors were irradiated with 681 nm laser light. TPs showed the highest efficacy in PDT in vivo. At doses of 0.5, 1.0, or 2.0 ug/g and irradiation with 30 J of 681 nm light, tumor growth delays comparable to those obtained at much higher doses (2.0 ug/g) and light energy (300 J) were obtained for the other PS tested in this work: Ph4-OH (N-Butanol-6-pheophorbamide) and MPPH (Hexyl ether of 6-methylpyropheophorbidea). TPs were found to be 10-20 times more potent photosensitizer compared to Ph4-OH and MPPH [137].  
Table 3 below shows information described in the article about the PDT mechanisms.  
\begin{table}
\begin{tabular}{c c c} \hline \hline
**Photosensitizer** & **Characteristic Information Described in the Article about the Mechanisms of** & **Article** \\  & **Action of Each Photosentizer** & \\ \hline Curcumine & Inhibits the NF-kB pathway. Can induce autophagy, inhibit EMT, and invasion and & [30] \\  & migration of tumor cells. & \\ \hline Hypericin & It can induce stress in the ER, leading to the release of calcium ions into the cytoplasm. & \\  & Increasing their levels can activate various enzymes and lead to mitochondrial & [46] \\  & damage. & \\ \hline Riboflavin & It can activate MAPK (mitogen-activated protein kinase) pathways such as p38 and & \\  & JNK, leading to further activation of apoptotic mechanisms. & [59] \\ \hline Phycocyanin & Depending on the dose of PS and light, it can activate either apoptosis or necrosis. & [67] \\ \hline Anthraquinones & Some anthraquinones may additionally inhibit the defense mechanisms of cancer cells, & [75] \\  & leading to the accumulation of ROS and increasing the effectiveness of PDT. & \\ \hline  & Cycloaddition occurs, and a covalent bond is formed between the psoralen and the & \\  & pyrimidine bases. During the subsequent phases of UV irradiation, additional & \\  & interactions can occur between the psoralen monoadduct and the pyrimidine base, & \\  & resulting in the formation of cross-links between DNA strands. & \\ \hline \hline \end{tabular}
\end{table}
Table 3: Characteristic information described in the article about the mechanisms of action of each photosensitizer.