Impact of Photosensitizers Activation on Intracellular Trafficking and Viscosity

Kelly Aubertin,François Gallet,Stéphanie Bonneau,Amanda K A Silva,Jean-Claude Bacri,Claire Wilhelm

doi:10.1371/journal.pone.0084850

Abstract

The intracellular microenvironment is essential for the efficiency of photo-induced therapies, as short-lived reactive oxygen species generated must diffuse through their intracellular surrounding medium to reach their cellular target. Here, by combining measurements of local cytoplasmic dissipation and active trafficking, we found that photosensitizers activation induced small changes in surrounding viscosity but a massive decrease in diffusion. These effects are the signature of a return to thermodynamic equilibrium of the system after photo-activation and correlated with depolymerization of the microtubule network, as shown in a reconstituted system. These mechanical measurements were performed with two intracellular photosensitizing chlorins having similar quantum yield of singlet oxygen production but different intracellular localizations (cytoplasmic for mTHPC, endosomal for TPCS2a). These two agents demonstrated different intracellular impact.

Highlights

Photodynamic therapy uses photo-activated organic molecules with very special photo-physical properties
Photochemical internalization (PCI) using the photoactivation of photosensitizers that localize in endosomes, induces endosomal membrane changes, enabling release into the cytosol of an active substance stored in the endosomal compartment [7,8]
M-THPC spreads in the cytoplasmic compartment, while TPCS2a is found in the endosomal compartments

Summary

Introduction

Photodynamic therapy uses photo-activated organic molecules (porphyrins, chlorins, phthalocyanins, etc.) with very special photo-physical properties Owing to their triplet state, irradiation of these photosensitizers generates reactive species such as singlet oxygen [1]. More marked changes occur if the photosensitizer is localized in the cytoplasm affecting mitochondria, endoplasmic reticulum or functional organelles - and potentially leading to cell death by necrosis or apoptosis [9,10]. This approach, called photodynamic therapy (PDT), is already used in the clinic for cancer treatment [11]

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Discussion

Conclusion