Efficacy of photochemical internalisation using disulfonated chlorin and porphyrin photosensitisers: An in vitro study in 2D and 3D prostate cancer models

Alejandra Martinez De Pinillos Bayona,Josephine H Woodhams,Hayley Pye,Rifat A Hamoudi,Caroline M Moore,Alexander J Macrobert

doi:10.1016/j.canlet.2017.02.018

Alejandra Martinez De Pinillos Bayona, Josephine H Woodhams + Show 4 more

Open Access

https://doi.org/10.1016/j.canlet.2017.02.018

Copy DOI

Abstract

This study shows the therapeutic outcome of Photochemical Internalisation (PCI) in prostate cancer in vitro surpasses that of Photodynamic Therapy (PDT) and could improve prostate PDT in the clinic, whilst avoiding chemotherapeutics side effects. In addition, the study assesses the potential of PCI with two different photosensitisers (TPCS2a and TPPS2a) in prostate cancer cells (human PC3 and rat MatLyLu) using standard 2D monolayer culture and 3D biomimetic model. Photosensitisers were used alone for photodynamic therapy (PDT) or with the cytotoxin saporin (PCI). TPPS2a and TPCS2a were shown to be located in discrete cytoplasmic vesicles before light treatment and redistribute into the cytosol upon light excitation. PC3 cells exhibit a higher uptake than MatLyLu cells for both photosensitisers. In the 2D model, PCI resulted in greater cell death than PDT alone in both cell lines. In 3D model, morphological changes were also observed. Saporin-based toxicity was negligible in PC3 cells, but pronounced in MatLyLu cells (IC50 = 18 nM). In conclusion, the study showed that tumour features such as tumour cell growth rate or interaction with drugs determine therapeutic conditions for optimal photochemical treatment in metastatic prostate cancer.

Highlights

Prostate cancer is the most common type of cancer affecting males and 4th leading cause of death from cancer [1]
Cellular fluorescence in PC3 and MatLyLu whole-cells increased with the PS dose in both cell lines, and a linear dose-dependency for both photosensitisers in PC3 and MatLyLu cells was seen (Fig. 1)
Previous in vitro studies have compared Photochemical Internalisation (PCI)-induced cytotoxicity using a variety of drugs and photosensitisers with the purely photooxidative effect caused by Photodynamic Therapy (PDT) [9,28e30]

Summary

Introduction

Prostate cancer is the most common type of cancer affecting males and 4th leading cause of death from cancer [1]. There is great interest in the development of focal treatments which can treat the more significant cancers whilst sparing healthy prostate tissue Both Photodynamic Therapy (PDT) and Photochemical Internalisation (PCI) are light-based focal therapies that use photosensitisers (PS) which upon interaction with molecular oxygen, and Bayona). PCI requires amphiphilic photosensitisers which can localise in the endosomal membrane after being internalised by cells via adsorptive endocytosis so that a photooxidative effect can be exerted in the membrane, leading to its rupture [4e6]. Features of both TPPS2a and TPCS2a fulfil these requirements

Objectives

Methods

Results

Conclusion