Porphyrin‐fullerene C₆₀ Dyads with High Ability to Form Photoinduced Charge‐separated State as Novel Sensitizers for Photodynamic Therapy^¶

Abstract

The photodynamic activities of a porphyrin‐C60 dyad (P‐C60) and its metal complex with Zn(II) (ZnP‐C60) were compared with 5‐(4‐acetamidophenyl)‐10,15,20‐tris(4‐methoxyphenyl)‐porphyrin (P), both in homogeneous medium‐bearing photooxidizable substrates and in vitro on the Hep‐2‐human‐larynx‐carcinoma cell line. This study represents the first evaluation of dyads, with a high capacity to form a photoinduced charge‐separated state, to act as agents to inactivate cells by photodynamic therapy (PDT). Absorption and fluorescence spectroscopic studies were performed in toluene and N,N‐dimethylformamide (DMF). The emission of the porphyrin moiety in the dyads is strongly quenched by the attached fullerene C60 moiety. The singlet molecular oxygen, O2(1Δg), productions (φΔ) were determined using 9,10‐dimethylanthracene (DMA). The values of φΔ were strongly dependent on the solvent's polarity. Comparable φΔ values were found for dyads and P in toluene, while O2(1Δg) production was significantly diminished for the dyads in DMF. In more polar solvent, the stabilization of charge‐transfer state takes place, decreasing the efficiency of porphyrin triplet‐state formation. Also, both dyads photosensitize the decomposition of L‐tryptophan in DMF. In biological medium, no dark cytotoxicity was observed using sensitizer concentrations ≤1 μM and 24 h of incubation. The uptake of sensitizers into Hep‐2 was studied using 1 μM of sensitizer and different times of incubation. Under these conditions, a value of ∼1.5 nmol/106 cells was found between 4 and 24 h of incubation. The cell survival after irradiation of the cells with visible light was dependent upon light‐exposure level. A higher photocytotoxic effect was observed for P‐C60, which inactivates 80% of cells after 15 min of irradiation. Moreover, both dyads keep a high photoactivity even under argon atmosphere. Thus, depending on the microenvironment where the sensitizer is localized, these compounds could produce biological photodamage through either an O2(1Δg)‐mediated photoreaction process or a free‐radicals mechanism under low oxygen concentration. These results show that molecular dyads, which can form a photoinduced charge‐separated state, are a promising model for phototherapeutic agents, with potential applications in cell inactivation by PDT.

Photodynamic therapy with fullerenes

“…Milanesi et al 78 compared PDT with a porphyrin-C 60 dyad (P-C 60 ) and its metal complex with Zn(II) (ZnP-C 60 ) were compared with 5-(4-acetamidophenyl)-10,15,20-tris(4-methoxyphenyl)porphyrin (P), both in homogeneous medium containing photooxidizable substrates and in vitro on the Hep-2 human larynx carcinoma cell line. 1 O 2 yields (Φ Δ ) were determined using 9,10-dimethylanthracene (DMA).…”

Intraperitoneal photodynamic therapy mediated by a fullerene in a mouse model of abdominal dissemination of colon adenocarcinoma

“…Although it has not yet been conclusively proven, it is possible that the highly reactive HO • is proportionately more cytotoxic than 1 O 2 on a molecule for molecule basis. Furthermore, it is reasonably well-accepted that type 1 photochemistry is less dependent on the surrounding oxygen concentration than is type 2 photochemistry (35,36). Fullerenes may be able to be relatively more effective in hypoxic tumors growing in such regions as the peritoneal cavity where pO2 levels are lower than in well-perfused tissues (37).…”

Graphene-Based Photodynamic Therapy and Overcoming Cancer Resistance Mechanisms: A Comprehensive Review

“…Milanesio et al compared the PDT effect of porphyrin-C60 and its metal complex with Zn(II) to the pure porphyrin (5-(4-acetamidophenyl)-10,15,20-tris(4-methoxyphenyl)-porphyrin) in Hep-2 cell line and concluded that the porphyrin-C60 complex had the greatest impact on cells. 379 …”

“…International Journal of Nanomedicine 2024:19 5660 porphyrin-C60 and its metal complex with Zn(II) to the pure porphyrin (5-(4-acetamidophenyl)-10,15,20-tris(4-methoxyphenyl)-porphyrin) in Hep-2 cell line and concluded that the porphyrin-C60 complex had the greatest impact on cells. 379 Miki et al reported the preparation of amphiphilic γ-cyclodextrin-fullerene complexes and Sugikawa et al described ROS generation. 375,380 With such molecules, it is also possible to prepare hybrid complexes of C60 and hydrophobic porphyrin by mixing in water in the presence of PEG.…”