## 2 Metallic Nanoparticles in Conjugation with Chlorin Derivatives
### Iron Oxide and Other Magnetic Nanoparticles  
Magnetic nanoparticles constitute one of the most frequently used metallic nanoparticles as drug delivery carriers. The surface coating for magnetic nanoparticles can be polyvinyl alcohol (PVA), dextran, polyethylene glycol (PEG), polyvinylpyrrolidone (PVP), or chitosan, which protect them from instant clearance within the bloodstream. There are many examples of magnetic nanoparticles with various chlorin conjugates with potential medical applications. An interesting example in this regard was proposed by [PERSON] et al., who prepared liposome-cargo particles (Figure 3) bearing iron oxide nanoparticles and a chlorin-based PS--temoporfin. Such a combination can be considered a further development of Foscan, a commercially available liposome formulation. Due to the combination of iron oxide nanoparticles and tempororfin, such a combination could be applied for magnetothermal treatment (MHT) and PDT [16]. The authors confirmed the stability of nanoparticles within 30 days of storage and later tested it, using an in vitro model, against ovarian cancer cells. The maximal iron uptake was achieved after a 1 h incubation, reaching 15-20 pg per cell. The studies indicated that iron nanoparticles were deposited in the membrane compartment and did not cross this barrier into the cytoplasm. Foscan crossed lipid bilayers and localized inside the cells due to its hydrophobic nature. The authors examined the potential of the combined magneto-phototherapy. They noted that only 10% of the cell population survived when treated with the magnetic field, whereas only 1% persisted when PDT was applied alone. Combining these modalities provided the complete elimination of the initial cell culture population. In parallel, the authors overlooked the impact of nanoparticles on cells when they were not activated. Additionally, the high potential of this liposome cargo was confirmed in in vivo trials using a mouse model. Particles were injected into the tumor, where the majority remained. Non-activated particles did not reveal any impact on the tumor, whereas turning on magnetotherapy and phototherapy alone induced partial cancer regression. Total regression was noted when both therapies were combined. It is believed that magnetotherapy potentiates PDT by increasing the tissue temperature. A higher temperature is the cause of blood vessel extension, thus improving blood flow through the tumor. Increased blood flow provides a higher partial molecular oxygen content in the tumor and its neighborhood. It is essential because molecular oxygen is a substrate for the excited PS in the photodynamic reaction, which leads to the formation of singlet oxygen--a highly reactive agent responsible for cancer cell death [16]. In another study, the theranostic properties of metallic nanoparticles bearing a PS were assessed by [PERSON] et al., who developed nanoparticles consisting of iron oxides (Fe\({}_{3}\)O\({}_{4}\)) and Ce\({}^{6}\) bonded together via an aliphatic linker (Figure 4) [17]. The authors confirmed the formation of singlet oxygen under particle irradiation. The system was applied in in vitro and in vivo studies based on gastric cancer cells and tumors (MGC803). The nanoparticles, at a concentration of 42 uM and excited with light at 632.8 nm with an energy density of 30 mW/cm\({}^{2}\) for 10 min, caused a decrease in cancer cell viability to <20%  
Figure 3: The schematic structure of the liposome–cargo magnetic particles with Foscan [16]. of the initial population. Moreover, the nanoparticles enabled cancerous visualization via NIR fluorescence and magnetic resonance imaging (MRI). Particles produced reasonable magnetic responses useful for MRI imaging, which was confirmed in a trial with a nude mouse model [17]. Various methods were used for the conjugation of PSs to magnetic nanoparticles. Quite a simple approach was proposed by [PERSON] et al.--they sonicated a mixture of Fe\({}_{3}\)O\({}_{4}\) nanoparticles and Ce6 in a toluene/water emulsion [18].