Properties of halogenated and sulfonated porphyrins relevant for the selection of photosensitizers in anticancer and antimicrobial therapies.

Barbara Pucelik,Robert Paczyński,Grzegorz Dubin,Mariette M Pereira,Janusz M Dąbrowski,Luis G Arnaut,Michael Hamblin

doi:10.1371/journal.pone.0185984

Barbara Pucelik, Robert Paczyński + Show 5 more

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https://doi.org/10.1371/journal.pone.0185984

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Journal: PloS one	Publication Date: Oct 10, 2017
Citations: 59	License type: CC BY 4.0

Affiliation: Jagiellonian University, University of Coimbra

Abstract

The impact of substituents on the photochemical and biological properties of tetraphenylporphyrin-based photosensitizers for photodynamic therapy of cancer (PDT) as well as photodynamic inactivation of microorganisms (PDI) was examined. Spectroscopic and physicochemical properties were related with therapeutic efficacy in PDT of cancer and PDI of microbial cells in vitro. Less polar halogenated, sulfonamide porphyrins were most readily taken up by cells compared to hydrophilic and anionic porphyrins. The uptake and PDT of a hydrophilic porphyrin was significantly enhanced with incorporation in polymeric micelles (Pluronic L121). Photodynamic inactivation studies were performed against Gram-positive (S. aureus, E. faecalis), Gram-negative bacteria (E. coli, P. aeruginosa, S. marcescens) and fungal yeast (C. albicans). We observed a 6 logs reduction of S. aureus after irradiation (10 J/cm2) in the presence of 20 μM of hydrophilic porphyrin, but this was not improved with incorporation in Pluronic L121. A 2–3 logs reduction was obtained for E. coli using similar doses, and a decrease of 3–4 logs was achieved for C. albicans. Rational substitution of tetraphenylporphyrins improves their photodynamic properties and informs on strategies to obtain photosensitizers for efficient PDT and PDI. However, the design of the photosensitizers must be accompanied by the development of tailored drug formulations.

Highlights

Photodynamic therapy (PDT) is a noninvasive and promising cancer treatment modality and has attracted considerable attention in recent years [1]
The broad range of photosensitizers employed in PDT and photodynamic inactivation of microorganisms (PDI) includes naturally occurring and synthetic compounds modified by various substitution patterns [4, 5]
We show that porphyrin derivatives offer a very convenient template to design and test phototherapeutic agents for PDT and PDI

Summary

Introduction

Photodynamic therapy (PDT) is a noninvasive and promising cancer treatment modality and has attracted considerable attention in recent years [1]. Modified tetrapyrrolic-based photosensitizers are highly attractive phototherapeutic agents for PDT of cancer, and for photodynamic inactivation of microorganisms (PDI). PDT is based on the generation of reactive oxygen species (ROS) in the biological target by a combination of light, a photosensitizer and molecular oxygen. There is an increasing appreciation of the need to integrate in molecular design insights emerging from studies of PS-target interactions, cellular signaling processes and increased resistance [6, 7]. Photophysical and photochemical properties of PS can be related with its behavior in biological systems, namely with aggregation, tumor type-specific PS uptake mechanisms, binding to plasma proteins or change in hydrophilicity/lipophilicity in given physiological environments

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