Cancer, Photodynamic Therapy and Porphyrin-Type Derivatives

Abstract

This review has two parts. The first one gives an approach to interdisciplinary studies against cancer carried out by many scientists using porphyrin-type substrates as photosensitizers in PDT. Intensive studies were performed for almost six decades. The successes really started in 1993 with the first formulation patented under the trade name Photofrin, which was immediately approved in several countries to treat certain types of cancer. Photofrin is still used although certain negative features soon became well known. That has motivated the search for better new photosensitizers. Several ones were developed, evaluated and a few of them had clinical approval. This group includes porphyrin derivatives and pro-drugs (aminolevulinic acid and its alkyl esters). Oncological, dermatological and ophthalmic applications are now taking place for the benefit of mankind. The second part of this review is related with the work carried out in Aveiro at the authors University on the synthesis and biological evaluation of several potential PDT photosensitizers. Not only new synthetic methodologies mainly for porphyrins and chlorins were developed but also other related macrocycles of the phthalocyanine and corrole types have entered in the same "pipeline". In vivo and in vitro biological evaluations also took place under interdisciplinary studies.

Synthesis, Characterization and Photodynamic Activity against Bladder Cancer Cells of Novel Triazole-Porphyrin Derivatives

“…These compounds are considered to be highly relevant in the medicinal field due to their high ability to act as photosensitizers in photodynamic therapy (PDT) [4]. In fact, porphyrins and analogues are special candidates for the management of oncological diseases by following the PDT therapy [5][6][7][8][9][10][11][12][13]. PDT is centered in a photooxidation process occurring in target tissues through three key components: photosensitizer (PS), oxygen, and light (sources emitting within the absorption spectrum of the PS) [14].…”

“…PDT is centered in a photooxidation process occurring in target tissues through three key components: photosensitizer (PS), oxygen, and light (sources emitting within the absorption spectrum of the PS) [14]. The combination of these components produces lethal cytotoxic agents [e.g., singlet oxygen ( 1 O 2 ) and/or other reactive oxygen species] that are responsible for the destruction of malignant cells [4,13,15,16] An obvious advantage of this therapeutic approach is that it is minimally invasive and consequently with great significance for improving patients' outcomes with either benign or malignant diseases [17]. The specificity of PDT relies on the preferential accumulation of the PS in the diseased tissue and on the localized light delivery, so the damaging should be confined to the irradiated area [14,18,19].…”

“…In recent years, several groups have been dedicated to the optimization of PDT by exploring methodologies that induce structural modifications on the porphyrinic macrocycle core, aiming to reach compounds with adequate photophysical and hydrophobic/hydrophilic properties and with high specificity for the tumor [13,17,21,22]. In fact, PDT efficiency can be enhanced by improving intracellular targeting ability of a PS [17].…”

“…In fact, PDT efficiency can be enhanced by improving intracellular targeting ability of a PS [17]. One of the approaches to reach this selectivity is based on the synthesis of porphyrins bearing targeting moieties, like carbohydrate units [13,15,19,[23][24][25][26], cyclodextrins [13,[27][28][29][30], human serum albumin and monoclonal antibodies [13,[31][32][33], among others. Other moieties that merit attention are based on triazoles.…”

Chemical approaches for the enhancement of porphyrin skeleton-based photodynamic therapy

“…As an effective combination therapeutic strategy, Photofrin V R did not display serious toxicity. Moreover, the survival period of inoperable tumour patients was prolonged, and the quality of life improved 9,10 . However, patients still suffered several side effects during the treatment, including skin photosensitivity and metabolic disturbances 10 .…”