Oncologic Photodynamic Therapy: Basic Principles, Current Clinical Status and Future Directions

Abstract

Photodynamic therapy (PDT) is a clinically approved cancer therapy, based on a photochemical reaction between a light activatable molecule or photosensitizer, light, and molecular oxygen. When these three harmless components are present together, reactive oxygen species are formed. These can directly damage cells and/or vasculature, and induce inflammatory and immune responses. PDT is a two-stage procedure, which starts with photosensitizer administration followed by a locally directed light exposure, with the aim of confined tumor destruction. Since its regulatory approval, over 30 years ago, PDT has been the subject of numerous studies and has proven to be an effective form of cancer therapy. This review provides an overview of the clinical trials conducted over the last 10 years, illustrating how PDT is applied in the clinic today. Furthermore, examples from ongoing clinical trials and the most recent preclinical studies are presented, to show the directions, in which PDT is headed, in the near and distant future. Despite the clinical success reported, PDT is still currently underutilized in the clinic. We also discuss the factors that hamper the exploration of this effective therapy and what should be changed to render it a more effective and more widely available option for patients.

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

“…The latter is of considerable importance because the short half-life of PSs ensures that the maximum ROS-mediated damage in PDT is achieved at a precise subcellular localisation (van Straten et al 2017). Some PSs exhibit preferential localisation in the ER, mitochondria, plasma membrane, lysosomes, or nucleic acids.…”

“…Photosensitisers currently approved for clinical use are mostly porphyrin-related, and, apart from HpD (Photofrin (Allison et al 2004;van Straten et al 2017). A significant number of photosensitisers are currently being tested in numerous clinical trials for the treatment of different types of tumours, age-related macular degeneration and various skin disorders (Wilson and Patterson 2008).…”

“…Despite having several advantages over conventional therapies, the use of PDT in cancer is so far limited to superficial or endoscope-accesible tumours, therefore primarily those situated in the skin, esophagous, stomach, bile duct, bladder, and lung (Wang et al 2001;Allison et al 2004;van Straten et al 2017). Moreover, even though numerous studies have demonstrated that PS can be used against essentially all types of microorganisms, PDT is infrequently used as antimicrobial treatment, except in limited scope in dermatology and dentistry (Kharkwal et al 2011).…”

PDGFRβ-specific affibody-directed delivery of a photosensitizer, IR700, is efficient for vascular-targeted photodynamic therapy of colorectal cancer

“…Unlike conventional chemotherapy, PDT involves a low risk of systematic toxicity and has thus been considered an ideal modality for the clinical treatment of cancers of the skin, brain, head, and neck, lung, esophagus, pancreas, bile duct, breast, bladder, prostate, stomach, colon, female reproductive tract, etc. (Shafirstein et al, 2017;van Straten et al, 2017).…”

Strategies for optimizing the delivery to tumors of macrocyclic photosensitizers used in photodynamic therapy (PDT)

“…In photodynamic therapy (PDT), visible light is used for killing diseased cells and tissues though the activation of a photosensitizing molecule (PS) that in the presence of oxygen generates reactive oxygen species (ROS) [1,2]. Different types of prokaryotic and eukaryotic cells can be killed with this modality provided that the PS has been taken up by the cell or is located in close proximity for allowing the generated ROS to interact with cellular substrates susceptible of photo-oxidative modifications [3,4].…”