4.2 Metal-modified porphyrin photosensitizers enhance light energy capture efficiency to enhance PDT
Metal-porphyrins are widely present in nature and their ability to cleave DNA nucleases has attracted significant attention in the last few years. Thus, combining porphyrins with metals not only provides additional antitumor activity and tumor selectivity, but also allows tracking the biodistribution of metals inside and outside tumor cells(Lovejoy and Lippard 2009). Due to paramagnetic effects, the photocatalytic activity of metal complexes is heavily dependent on the central metal(Zhang et al. 2019c). Therefore, many researchers have inserted metals into porphyrin rings to maintain the stability and photophysical properties of the porphyrin ring. In addition, the structure of β-substituted porphyrins is closer to that of natural porphyrins and has been widely used in biological research(Zhou et al. 1996). In these studies, some transition metal compounds, such as iridium, ruthenium, rhenium, and osmium compounds, were investigated to have good antitumor activity, especially in the field of photodynamics(Imberti et al. 2020; Xie et al. 2021; Zhang et al. 2019a; Zhu et al. 2019c). Ru is less toxic to normal cells and its use in PDT is very attractive(Schmitt et al. 2008; Schmitt et al. 2009).
Schmitt and co-workers synthesized four aromatic Ru(II) derivatives (the aromatics are C6H5Me orp -PriC6H4Me), Mononuclear 5-(4-pyridyl)-10,15,20-triphenylporphyrin, 5-(3-pyridyl)-10,15,20-triphenylporphyrin, tetranuclear 5,10,15,20-tetra(4-pyridyl)porphyrin (tetra-4-pp), 5,10,15,20-tetra(3-pyridyl) porphyrin) (tetra-3-pp) and evaluated them as potential dual photosensitizers and chemotherapeutic agents against human melanoma cells Me300(Schmitt et al. 2009). The results showed that the uptake and high photosensitizing activity of metal Ru on human melanoma cell models were promoted under red light (652 nm) irradiation at only 5 J/cm2. In another study, Zhang and co-workers synthesized porphyrin derivatives containing Ru(II) polypyridyl porphyrins and zinc(II) porphyrin structures and evaluated their cytotoxicity against human nasopharyngeal carcinoma HK-1 and cervical cancer HeLa cells(Zhang et al. 2011). The results showed that the porphyrins containing Ru had high1O2 quantum yields, rapid cellular uptake, low dark cytotoxicity and potent photocytotoxicity (80% of Ru-L-containing incubated HK-1 cells were killed at a concentration of 1 μM and a yellow light dose of 3 J/cm2).