# Advances in Purpurin 18 Research: On Cancer Therapy
## 4 Photodynamic Therapy
Since gold nanoparticles (GNPs) represent a promising system for pu18 delivery and ensure better entry into tumor cells, recently the group of [PERSON] et al. [42] utilized this tool. They synthesized ionic liquid (IL)-dependent GNPs with pu18 (Figure 4B). This system is based on the properties of water-soluble ILs that can promote increased solubility of conjugated PSs [42]. It has also been reported that ILs can increase drug stability, promote drug delivery, and controlled release [43]. The prepared drugs consisted of IL-type PSs (PS1 = pu18 + morpholinium, PS2 = pu18 + imidazolium), which were incorporated into GNPs (GNP1 contains 492 nmol\(\cdot\)mg\({}^{-1}\) PS1 and GNP2 contains 573 nmol\(\cdot\)mg\({}^{-1}\) PS2) to give 20-60 nm large spherical particles. The phototoxicity of the newly prepared GNP1 and GNP2 was verified using the A549 cell line and illumination with a light-emitting diode (735-785 nm, 2 J\(\cdot\)cm\({}^{-2}\), 15 min). In the case of GNP1, a 34- and 37-fold increase in phototoxicity was observed compared to free PS1 (12 and 24 h after photoactivation, constant IC\({}_{50}\) = 0.38 g\(\cdot\)mL\({}^{-1}\)) and no observable dark toxicity. Besides, microscopic analysis of GNP1-treated cells in combination with light showed the presence of apoptotic bodies. In contrast, GNP2 showed low phototoxicity at 12 h after illumination (IC\({}_{50}\) > 20 ug\(\cdot\)mL\({}^{-1}\)) and after 24 h, only 3.6-fold higher phototoxicity (IC\({}_{50}\) = 4.34 ug\(\cdot\)mL\({}^{-1}\)) compared to free PS2. Besides, moderate dark toxicity was determined for both GNP2 and PS2. Thus, it is clear that in the formation of nanoparticles, the type of IL used, and its properties were of great importance. Figure 4: Various types of modifications of purpurin 18 (pu18) may lead to an improvement in its properties as a photosensizer for use in photodynamic therapy. (**A**) The first approach is to use a suitable carrier such as graphene oxide (GO) to increase the bioavailability of pu18. In this case, two types of GO nanoparticles were prepared with pu18-N-ethylamine (pu18 NEA) and a photosensitizer (PS), via covalent (GO–PS2) and non-covalent bonds (GO–PS3). (**B**) Another type of nanoparticles is based on the properties of ionic liquids (IL), which together with pu18 were incorporated into gold nanoparticles (GNP1 and GNP2) and the structure of pu18-methyl ester (pu18 Me). (**C**) Improved PS retention in tumor cells was observed in the case of conjugated drug pu18 with the amine spermine. In the case of the attachment of a poly(ethylene) glycol (PEG) spacer, an increase in hydrophobicity and an improvement in the bioavailability of PS were observed [44]. Nanoparticles can also play an important role in targeted drug delivery to minimize treatment side effects. As an example, SiO\({}_{2}\) nanoparticles (SiO\({}_{2}\)NPs) [45] have several advantages, in particular, nontoxicity and high stability as well as compatibility with various PSs including pu18, chlorine [46], methylene blue [47], and hematoporphyrin [48; 49]. The group of [PERSON] et al. used mesenchymal stem cells (MSCs) as pu18 transporters in the form of PS-SiO\({}_{2}\)NPs nanoparticles for targeting breast cancer tumor cells [45]. It is known that MSCs naturally show a high affinity for tumor cells [50; 51]. The generated PS-SiO\({}_{2}\)NPs-MSCs particles migrated to human breast cancer cells (MCF-7), which means that the content of PS-SiO\({}_{2}\)NPs does not negatively affect the targeting of MSCs and pu18 can thus be accumulated in targeted cells. At the same time, it was found that PS-SiO\({}_{2}\)NPs-MSCs inhibited the growth of MCF-7 cells after PDT treatment, both in the form of 2D culture in vitro and in vivo in nude mice with subcutaneously transplanted MCF-7 cells, in which there was a reduction in tumor size and weight.