Photostable Platinated Bacteriochlorins as Potent Photodynamic Agents

Abstract

Photodynamic therapy (PDT) is used to treat various cancerous diseases. Recently, we have demonstrated that platinated pyridyl-substituted porphyrins are potent agents for PDT with very high phototoxicity (IC 50 down to 17 nM) and excellent phototoxic indices of higher than 5800 (p.i. = IC 50 (dark)/IC 50 (light)) [Rubbiani, R. et al., Chem. Commun. 2020, 56, 14373]. However, the absorption of porphyrins is not ideal for the treatment of larger tumors because they essentially do not absorb light between 650 and 850 nm. Herein, we report stable conjugates of a novel bacteriochlorin with cisplatin and transplatin. They exhibit extremely high phototoxicity (IC 50 values down to 6 nM, irradiated with a 750 nm LED at a fluence of 5 J/cm 2 ), very low dark toxicity, and thereby extremely high phototoxic indices up to 8300. Based on these exciting results, we believe that platinated bacteriochlorins are promising candidates for further investigation as novel PDT anticancer agents.

Low-Dose Near-Infrared Light-Activated Mitochondria-Targeting Photosensitizers for PDT Cancer Therapy

“…An important parameter to evaluate the effect of PSs is the phototoxic index (p.i. ), i.e., the ratio of dark to light toxicity [ 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 ]. Reducing the lipophilicity and minimizing aggregation of the planar PS, for example by PEGylation, plays a critical role for improving PDT therapeutic efficiency and improving the p.i.…”

“…The supporting information can be downloaded at: . References [ 9 , 26 , 33 , 40 , 43 , 66 , 67 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 ] are cited in the supplementary materials.…”

BODIPY-Based Photothermal Agents for Cancer Treatment

“…S2) of 1a, 1b, 2a, 2b, 3a, and 3b were determined by applying light at a wavelength of 630 nm (Fig. S2) based on a direct method 34,[37][38][39][40] The absorption maximum of all studied compounds is in the range between 588 and 617 nm in MeOH and the fluorescence emission maximum between 620 and 655 nm. In MeOH, DCM and toluene all compounds exhibit a rather sharp absorption maximum, while in H2O the absorption peak is very broad with distinctly lower extinction coefficients compared to the other solvents.…”

Potent PBS/Polysorbate-Soluble Transplatin-Derived Porphyrin-Based Photosensitizers for Photodynamic Therapy

“…These PSs are used in clinical settings for PDT due to their selectivity for malignant tissue, together with excellent photophysical properties . The initial idea of coupling platinum complexes to porphyrins , and porphyrin-related compounds − emerged from an anticipated dual-chemotherapeutic effect. However, our porphyrin PSs turned out to be extremely phototoxic with IC 50 values as low as 0.04 μM upon irradiation in HeLa cells but showing extremely low toxicities in the dark.…”