Combination of PDT and NOPDT with a Tailored BODIPY Derivative.

Loretta Lazzarato,Marco Blangetti,Roberta Fruttero,Giulia Maria Picone,Salvatore Sortino,Chiara Riganti,Alberto Gasco,Federica Sodano,Elena Gazzano,Aurore Fraix

doi:10.3390/antiox8110531

Loretta Lazzarato, Marco Blangetti + Show 8 more

Open Access

https://doi.org/10.3390/antiox8110531

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Journal: Antioxidants	Publication Date: Nov 7, 2019
Citations: 13	License type: CC BY 4.0

Affiliation: University of Turin, University of Catania

Abstract

The engineering of photosensitizers (PS) for photodynamic therapy (PDT) with nitric oxide (NO) photodonors (NOPD) is broadening the horizons for new and yet to be fully explored unconventional anticancer treatment modalities that are entirely controlled by light stimuli. In this work, we report a tailored boron-dipyrromethene (BODIPY) derivative that acts as a PS and a NOPD simultaneously upon single photon excitation with highly biocompatible green light. The photogeneration of the two key species for PDT and NOPDT, singlet oxygen (1O2) and NO, has been demonstrated by their direct detection, while the formation of NO is shown not to be dependent on the presence of oxygen. Biological studies carried out using A375 and SKMEL28 cancer cell lines, with the aid of suitable model compounds that are based on the same BODIPY light harvesting core, unambiguously reveal the combined action of 1O2 and NO in inducing amplified cancer cell mortality exclusively under irradiation with visible green light.

Highlights

Photodynamic therapy (PDT) for cancer involves the combined use of nontoxic photosensitizers (PSs) and visible light of appropriate wavelength [1,2]
These findings account for a photodegradation mechanism that is similar to the one that has already been observed for the non-iodinate analogue 1 [26], and that involves the heterolytic rupture of the C-O bond, with the consequent formation of a BODIPY-methyl carbocation via solvent substitution
With the aid of analogue derivative 1, which exclusively photogenerates nitric oxide (NO), and two suitable model compounds based on the same BODIPY core, we have provided evidence that the in vitro cytotoxic activity observed upon green light irradiation of 2 against human melanoma cell lines is due to the combined action of NO and 1 O2, whereas only NO is involved in the antiproliferative effects induced by 1

Summary

Introduction

Photodynamic therapy (PDT) for cancer involves the combined use of nontoxic photosensitizers (PSs) and visible light of appropriate wavelength [1,2]. PSs reach the lowest excited singlet state (1 PS*) and, after intersystem crossing (ISC), their lowest-energy excited triplet state (3 PS*). Due to their long lifetime (μs-ms), the 3 PS* can dissipate most of their energy via quenching with nearby molecular oxygen, potentially giving rise to two different reactions. This, in turn, can eventually generate the highly reactive and toxic hydroxyl radical (OH) These species are collectively called reactive oxygen species (ROS). The second (Type II reaction) entails energy transfer from 3 PS* to 3 O2 with the production of another ROS, highly toxic singlet oxygen (1 O2 ), which is the key species in PDT [2,3]. The local irradiation of a tumor after the systemic administration of PS can, lead to a burst of cytotoxic

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