## 2 Metallic Nanoparticles in Conjugation with Chlorin Derivatives
### Other Metallic Nanoparticles
In addition, other metals can be used as metallic nanoplatforms to develop multifunctional nanoagents. [PERSON] et al. used MoS2 two-dimensional nanosheets as a delivery platform for Ce6 [55]. Firstly, MoS2 was exfoliated chemically to obtain the binding side for lipoic acid-terminated polyethylene glycol. Nanosheets bearing PEG chains were conjugated to the photosensitizer via physical adsorption with a loading capacity of ca. 30% (Ce6:MoS2 weight ratio). Nanoplatforms loaded with Ce6 did not emit any fluorescence, but their singlet oxygen-generation ability was slightly lower than that of unbound Ce6. The authors performed experiments concerning the activity of MoS2-PEG/Ce6 against 4T1 cancer cells using both in vitro and in vivo models. They concluded that the irradiation of cells with light at 808 nm produced a photothermal effect and also enhanced the photodynamic therapy effect (triggered at 660 nm). The MoS2 nanoparticles irradiated with NIR light generated a temperature increase to ca. 43 \({}^{\circ}\)C, which also improved the cellular uptake of Ce6 molecules. High cellular uptake was assessed by the more intense intracellular fluorescence produced by Ce6 bound to the MoS2-PEG platform compared to Ce6 alone. In the in vivo trials, no adverse effect was observed after the intravenous injection of MoS2-PEG/Ce6. Moreover, significant tumor growth inhibition was noted under combined PTT and PDT treatment [55]. Bismuth sulfide nanostar-based nanoparticles were developed by [PERSON] et al. [56]. The authors functionalized Bi2S3 nanospheres with PEG to form nanostars. A highly porous star structure was functionalized with doxorubicin for chemotherapy and Ce6 for photodynamic therapy, and subsequently, the release of both molecules was evaluated. The authors found that doxorubicin can be released from nanostars in two ways: (_i_) after the decrease in pH (low pH is present in cancer tissues) and (_ii_) upon light activation. The anticancer potential of the obtained nanomaterial was assessed in vitro using HeLa and 4T1 cancer cell lines. Efficient uptake of 97.4% of nanoparticles inside both HeLa and 4T1 cell lines after 6 h of incubation was detected. The authors also estimated biocompatibility. Nanoparticles up to the concentration of 200 ug/mL were incubated with HUVECs and with L929 mouse fibroblasts. Above 80% cell viability was noted, which suggests acceptable biocompatibility. Intracellular ROS production was confirmed with the DCFH-DA assay. In the in vitro experiments, the decrease in cancer cell viability (HeLa and 4T1) as a result of PTT/PDT/chemotherapy combined treatment was observed. Moreover, significant mitochondrial defects were observed with nanoparticles as a result of PTT/PDT treatment, as well as a prolonged body circulation half-time in comparison to that with doxorubicin only, which resulted in a higher tumor uptake rate. In the in vivo model, BALB/c mice bearing 4T1 tumors were used. The experiments in vivo proved that nanostars caused low systemic toxicity and organ damage. In these studies, the high potential of studied nanoparticles for computed tomography and fluorescence imaging, as well as the remarkable regression of the tumor, was also observed [56]. [PERSON] et al. presented nanosheets consisting of Hf and 5,15-di(_p_-methylbenzoate)chlorin (Me2 DBC) as a linker for colon cancer photodynamic therapy [57]. The obtained nanoparticles revealed 11-fold higher light absorption in the Q band range when compared to that with the porphyrin analog and produced singlet oxygen more efficiently. Their photodynamic activity potential was assessed using in vitro and in vivo models with murine (CT26 cells) and human (HT29 cells) colorectal cancers. In these studies, excitation light at a 640 nm wavelength and a dose of 90 J/cm\({}^{2}\) for in vitro experiments were applied, whereas 90 and 180 J/cm\({}^{2}\) were used for in vivo tests. The photoactivities of chlorin and porphyrin only, as well as the obtained nanosheets conjugated with chlorin and with porphyrin, were studied.