Photodynamic activity of Sn(IV) meso-tetraacenaphthylporphyrin and its methyl-β-cyclodextrin inclusion complexes on MCF-7 breast cancer cells

Abstract

A novel Sn(IV) meso-tetraacenaphthylporphyrin (SnTAcP) has been synthesized and characterized. SnTAcP was complexed with methyl-[Formula: see text]-cyclodextrin (m[Formula: see text]-CD), a nanocarrier that enhances water solubility, and the complexes were evaluated as PDT agents using MCF-7 breast cancer cells. A relatively low singlet oxygen quantum yield value of 0.36 was obtained in DMF, and the lowest energy Q band lies at 608 nm on the edge of the therapeutic window. SnTAcP was found to be non-toxic in the dark and phototoxic towards MCF-7 breast cancer cells with a half-maximal inhibitory concentration (IC[Formula: see text] value of 11 ± 1.1 [Formula: see text]g · mL[Formula: see text] after 30 min of irradiation with a 625 nm Thorlabs LED that provides a dose of 432 J · cm[Formula: see text]. A higher IC[Formula: see text] value of 21 ± 1.1 [Formula: see text]g · mL-1 was obtained for the m[Formula: see text]-CD inclusion complex of SnTAcP.

A Sn(iv) porphyrin with mitochondria targeting properties for enhanced photodynamic activity against MCF-7 cells

“…Porphyrin-related photosensitizers that have been developed for PDT, such as Photofrin®, Foscan® and 5,10,15,20- tetrakis (4-hydroxyphenyl)porphyrin ( p -THPP), and hypericin have previously been used as positive controls in this context, 30,31 but this is now routinely omitted. 8,9,11,13 Since SnP and SnPH have similar Φ Δ values, the difference in PDT activity cells can be attributed to the higher cellular uptake observed for SnPH . A comparison of the IC 50 values of SnP , SnPH with those reported previously for SnTTP , SnTPP , SnM , SnH (Scheme 2), cisplatin, and Photofrin (Table 2) highlights the enhanced PDT activity observed for SnPH .…”

“…a12 h incubation in the dark.b12 h incubation in the dark followed by exposure to a Thorlabs M625L3 LED (240 mW cm −2 , 20 min).cPI = phototoxic index (toxicity ratio of dark and light IC 50 values).dBy the shake-flask method.eIC 50 and PI values from ref. 8a (625 nm, Thorlabs M625L3 LED, 240 mW cm −2 , 20 min).…”

“…Metallation of porphyrins with Sn 4+ , Zn 2+ , Pt 2+ , Pd 2+ , or In 3+ facilitates the ISC process due to the heavy atom effect, enhancing the Φ Δ value. 4–9 Purlytin®, a Sn( iv ) ethyl etiopurpurin complex, has previously been reported to be an excellent second-generation photosensitizer during clinical trials. 1,2 a In recent years, a wide range of readily synthesized Sn( iv ) porphyrins and their corrole, chlorin and N-confused analogues have been reported to be potentially suitable for use as photosensitizer dyes in PDT and photodynamic antimicrobial chemotherapy both by our group and other researchers, 8–13 because trans -axial ligation hinders aggregation effects due to π–π stacking that can interfere with the photophysical properties of porphyrinoid dyes.…”

“…4–9 Purlytin®, a Sn( iv ) ethyl etiopurpurin complex, has previously been reported to be an excellent second-generation photosensitizer during clinical trials. 1,2 a In recent years, a wide range of readily synthesized Sn( iv ) porphyrins and their corrole, chlorin and N-confused analogues have been reported to be potentially suitable for use as photosensitizer dyes in PDT and photodynamic antimicrobial chemotherapy both by our group and other researchers, 8–13 because trans -axial ligation hinders aggregation effects due to π–π stacking that can interfere with the photophysical properties of porphyrinoid dyes. 8 The goal of this research is to identify efficient photosensitizer dyes with facile syntheses that can be readily scaled up for use in PDT.…”

“…The Sn( iv ) porphyrin analogues studied for biomedical singlet oxygen applications to date have lacked specific organelle targeting ability. 8–13 In this study, we examine whether dyes of this type can be further functionalized to enhance their suitability for use in hypoxic conditions. Photosensitizers that target mitochondria are reported to have better PDT efficacy than those that localize at other cellular sites.…”