Enhanced Cellular Uptake and Photodynamic Effect with Amphiphilic Fluorinated Porphyrins: The Role of Sulfoester Groups and the Nature of Reactive Oxygen Species

Barbara Pucelik,Adam Sułek,Mariette M Pereira,Grażyna Stochel,Luis G Arnaut,Sara M A Pinto,Agnieszka Drozd,Janusz M Dąbrowski

doi:10.3390/ijms21082786

Abstract

A class of amphiphilic photosensitizers for photodynamic therapy (PDT) was developed. Sulfonate esters of modified porphyrins bearing—F substituents in the ortho positions of the phenyl rings have adequate properties for PDT, including absorption in the red, increased cellular uptake, favorable intracellular localization, low cytotoxicity, and high phototoxicity against A549 (human lung adenocarcinoma) and CT26 (murine colon carcinoma) cells. Moreover, the role of type I and type II photochemical processes was assessed by fluorescent probes specific for various reactive oxygen species (ROS). The photodynamic effect is improved not only by enhanced cellular uptake but also by the high generation of both singlet oxygen and oxygen-centered radicals. All of the presented results support the idea that the rational design of photosensitizers for PDT can be further improved by better understanding the determinants affecting its therapeutic efficiency and explain how smart structural modifications can make them suitable photosensitizers for application in PDT.

Highlights

Photodynamic therapy (PDT) employs a photoactive molecule named a photosensitizer (PS), light absorbed by the PS and the molecular oxygen present in tissues to generate reactive oxygen species (ROS) [1]
In order to synthesize the desired fluorinated amphiphilic porphyrins, containing sulfonate ester appendices, the derivatization of 5,10,15,20-tetrakis(2-fluorophenyl)porphyrin and 5,10,15,20-tetrakis(2,6-difluorophenyl)porphyrin into the corresponding chlorosulfonated porphyrins was achieved by mixing the porphyrins with an excess of chlorosulfonic acid
The properties of sulfonate ester fluorinated porphyrins were examined to investigate the potential of this molecular template for PDT

Summary

Introduction

Photodynamic therapy (PDT) employs a photoactive molecule named a photosensitizer (PS), light absorbed by the PS and the molecular oxygen present in tissues to generate reactive oxygen species (ROS) [1]. ROS, such as singlet oxygen, superoxide ion, or hydroxyl radical, lead to the oxidation of biologically relevant molecules and cause irreversible destruction of target tissues by cell death, vascular damage, and inflammation. ROS may be generated by transferring an electron or hydrogen atom (type I processes) or electronic energy (type II processes) to molecular oxygen, with the formation of oxygen-centered radicals (superoxide ion and hydroxyl radicals) and singlet oxygen, respectively

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Results

Conclusion