Cyanoarylporphyrazines with High Viscosity Sensitivity: A Step towards Dosimetry-Assisted Photodynamic Cancer Treatment.

Irina V Balalaeva,Nina N Peskova,Dmitri V Krysko,Maria V Vedunova,Tatiana A Mishchenko,Natalia Y Shilyagina,Larisa G Klapshina,Vladimir I Plekhanov,Victoria D Turubanova,Svetlana A Lermontova

doi:10.3390/molecules26195816

Abstract

Despite the significant relevance of photodynamic therapy (PDT) as an efficient strategy for primary and adjuvant anticancer treatment, several challenges compromise its efficiency. In order to develop an “ideal photosensitizer” and the requirements applied to photosensitizers for PDT, there is still a need for new photodynamic agents with improved photophysical and photobiological properties. In this study, we performed a detailed characterization of two tetracyanotetra(aryl)porphyrazine dyes with 4-biphenyl (pz II) and 4-diethylaminophenyl (pz IV) groups in the periphery of the porphyrazine macrocycle. Photophysical properties, namely, fluorescence quantum yield and lifetime of both photosensitizers, demonstrate extremely high dependence on the viscosity of the environment, which enables them to be used as viscosity sensors. Pz II and pz IV easily enter cancer cells and efficiently induce cell death under light irradiation. Using fluorescence lifetime imaging microscopy, we demonstrated the possibility of assessing local intracellular viscosity and visualizing viscosity changes driven by PDT treatment with the compounds. Thus, pz II and pz IV combine the features of potent photodynamic agents and viscosity sensors. These data suggest that the unique properties of the compounds provide a tool for PDT dosimetry and tailoring the PDT treatment regimen to the individual characteristics of each patient.

Highlights

The past decade has witnessed major breakthroughs in photodynamic therapy (PDT) as an efficient strategy for primary and adjuvant anticancer treatment
Using fluorescence lifetime imaging microscopy (FLIM), we demonstrated the possibility of assessing local intracellular viscosity using porphyrazine dyes with 4-biphenyl (pz II) and pz IV as viscosity sensors and tracking the viscosity changes driven by PDT treatment
We present two photo-active dyes of the tetracyanotetra(aryl)porphyrazine group, pz II and pz IV, that combine the properties of potent photosensitizers with viscosity sensors

Summary

Introduction

The past decade has witnessed major breakthroughs in photodynamic therapy (PDT) as an efficient strategy for primary and adjuvant anticancer treatment. Despite significant progress in PDT, there are still several challenges that compromise its efficiency. Oxygen deficiency (hypoxia) in the tumor microenvironment can significantly diminish PDT efficiency for solid tumors [1,14,15]. Insufficient selectivity of the photosensitizer to the tumor and its accumulation in normal organs and tissues, especially skin and eyes, lead to undesirable photoinduced side effects [8,16,17]. Several types of tumors often become resistant to apoptotic and necroptotic cell death modalities, making their induction by PDT no longer an option [18,19]. There is still a need for new photosensitizers with improved photodynamic properties and less cytotoxic effects for normal tissues

Methods

Results

Discussion

Conclusion