Photodynamic Therapy and the Development of Metal-Based Photosensitisers

Abstract

Photodynamic therapy (PDT) is a treatment modality that has been used in the successful treatment of a number of diseases and disorders, including age-related macular degeneration (AMD), psoriasis, and certain cancers. PDT uses a combination of a selectively localised light-sensitive drug (known as a photosensitiser) and light of an appropriate wavelength. The light-activated form of the drug reacts with molecular oxygen to produce reactive oxygen species (ROS) and radicals; in a biological environment these toxic species can interact with cellular constituents causing biochemical disruption to the cell. If the homeostasis of the cell is altered significantly then the cell enters the process of cell death. The first photosensitiser to gain regulatory approval for clinical PDT was Photofrin. Unfortunately, Photofrin has a number of associated disadvantages, particularly pro-longed patient photosensitivity. To try and overcome these disadvantages second and third generation photosensitisers have been developed and investigated. This Review highlights the key photosensitisers investigated, with particular attention paid to the metallated and non-metallated cyclic tetrapyrrolic derivatives that have been studied in vitro and in vivo; those which have entered clinical trials; and those that are currently in use in the clinic for PDT.

Porphyrin-based cationic amphiphilic photosensitisers as potential anticancer, antimicrobial and immunosuppressive agents

“…Some of them, such as chlorin and bacteriochlorin derivatives, also exhibit an improved absorption in the red-light region (Berg et al 2005). However, many photosensitisers of the second generation are still not selective enough to reduce or prevent the undesirable side-effects associated with generalised skin photosensitivity (Ackroyd et al 2001;Josefsen and Boyle 2008).…”

“…This fact seems mostly relevant for phthalocyanines and texaphyrins that are better PSs when existing as diamagnetic complexes rather than in paramagnetic or free base forms. However, the most efficient porphyrin PSs are metal-free (Josefsen and Boyle 2008). Amongst metalloporphyrins, those with manganese(II) are interesting as contrast agents for magnetic resonance imaging (MRI) (Ali and van Lier 1999).…”

Phthalocyanine-loaded graphene nanoplatform for imaging-guided combinatorial phototherapy

“…12,13 However, most of these agents are not cancerspecific, are very hydrophobic, and are not easy to formulate. 14 To overcome these barriers and provide additional PTT capability, several delivery systems, based on gold nanoparticles, gold nanorods, and graphene, have been reported. 15,16 Among them, graphene is a highly promising nanomaterial for the development of PDT-PTT nanomedicine platforms.…”

Duramycin-porphyrin conjugates for targeting of tumour cells using photodynamic therapy

“…Through the possibility of targeted irradiance the duramycin-porphyrin conjugate could allow for specific death of the tumour and therefore reduce the risk of collateral damage to surrounding normal tissue. Photodynamic effect usually occurs very close to the localisation of the PS [25] and when the PS's binding site is the plasma membrane necrotic cell death can very rapidly follow irradiation [82]. As the duramycin-porphyrin conjugate binds to cancer cell membranes it is possible that cell death occurs via rapid necrosis which may reduce the risk of PDT-induced cytoprotective mechanisms.…”