Phosphinatophenylporphyrins tailored for high photodynamic efficacy

Abstract

The development of effective photosensitizers is particularly attractive for photodynamic therapy of cancer. Three novel porphyrin photosensitizers functionalized with phosphinic groups were synthesized and their physicochemical, photophysical, and photobiological properties were collected. Phosphinic acid groups (R1R2POOH) attached to the porphyrin moiety (R1) contain different R2 substituents (methyl, isopropyl, phenyl in this study). The presence of phosphinic groups does not influence absorption and photophysical properties of the porphyrin units, including the O2(1Δg) productivity. In vitro studies show that these porphyrins accumulate in cancer cells, are inherently nontoxic, however, exhibit high phototoxicity upon irradiation with visible light with their phototoxic efficacy tuned by R2 substituents on the phosphorus centre. Thus, phosphinatophenylporphyrin with isopropyl substituents has the strongest photodynamic efficacy due to the most efficient cellular uptake. We demonstrate that these porphyrins are attractive candidates for photodynamic applications since their photodynamic efficacy can be easily tuned by the R2 substituent.

Molybdenum cluster loaded PLGA nanoparticles as efficient tools against epithelial ovarian cancer

“…The photodynamic toxicity was evaluated upon light irradiation (365 nm) after 6 h incubation time without serum to avoid interactions of the nanoparticles with serum proteins that are limiting the biological application (Hynek et al, 2018).…”

The nanoscaled metal-organic framework ICR-2 as a carrier of porphyrins for photodynamic therapy

“…Interestingly, the photodynamic activity on HeLa cells strongly depends on the R substituent at the P atom, i.e., only the phenyl substituent (TPPPi(Ph)) ensured high phototoxicity, comparable with the best MOF systems. This feature does not seem to arise from the differences in singlet oxygen photosensitizing ability [ 26 ], but can be assigned to the differences in the biological properties provided by the substituent of the unbounded phosphinic groups at the surface of the composite nanoparticles. Unfortunately, the elucidation of the structure–activity relationship is rendered difficult due to the instability of the nanoICR-2/porphyrin nanoparticles in PBS media, as also observed for Zr-based MOFs.…”

“…Phenylene-1,4-bis(methylphosphinic acid) was prepared according to [ 25 ]. Phosphinic acid porphyrins 5,10,15,20-tetrakis(4-methylphosphinatophenyl)porphyrin (TPPPi(Me)), 5,10,15,20-tetrakis(4-isopropylphosphinatophenyl)porphyrin (TPPPi(iPr)), and 5,10,15,20-tetrakis(4-phenylphosphinatophenyl)porphyrin (TPPPi(Ph)) were prepared according to [ 26 ].…”

Chemical approaches for the enhancement of porphyrin skeleton-based photodynamic therapy

“…Recently, Hynek et al 26 first synthesised porphyrin derivatives containing four phosphinic functional groups with methyl, isopropyl and phenyl groups on phosphorus atoms. These compounds were evaluated for their in vitro anticancer activity against the HeLa cell line.…”

“…Structural modification of heteroatoms by introducing chalcogen atoms, such as sulphur and selenium, significantly changes the photophysical properties of compounds 27 . The incorporation of ionic groups such as pyridinium, sulphonate, carboxylate or phosphonate around the porphyrin is an effective method to address solubility issues and prevent aggregations 26 .…”