Photodynamic Therapy: Current Status and Future Directions

Abstract

Photodynamic therapy (PDT) is a minimally invasive therapeutic modality used for the management of a variety of cancers and benign diseases. The destruction of unwanted cells and tissues in PDT is achieved by the use of visible or near-infrared radiation to activate a light-absorbing compound (a photosensitizer, PS), which, in the presence of molecular oxygen, leads to the production of singlet oxygen and other reactive oxygen species. These cytotoxic species damage and kill target cells. The development of new PSs with properties optimized for PDT applications is crucial for the improvement of the therapeutic outcome. This review outlines the principles of PDT and discusses the relationship between the structure and physicochemical properties of a PS, its cellular uptake and subcellular localization, and its effect on PDT outcome and efficacy.

Nitric oxide antagonism to glioblastoma photodynamic therapy and mitigation thereof by BET bromodomain inhibitor JQ1

“…1B; ~50% apoptosis). In contrast, relatively little necrotic cell death occurred (<5%), which is significant because clinical PDT strives to maximize apoptosis and minimize necrosis in order to limit non-specific inflammatory stress from necrosis (12)(13)(14). Based on our previous evidence obtained with breast cancer cells (21-23), we predicted that PDT would activate PI3K-dependent Akt in U87 cells upstream of NF-κB activation and iNOS/NO expression.…”

“…In addition to improving average survival time relative to cisplatin-based chemotherapy, for example (69), PDT has the advantage of high tumor-site specificity, i.e. fewer negative off-target effects on normal tissue (12)(13)(14). However, like other therapeutic interventions, PDT can be antagonized by pre-existing or stress-induced factors which could increase cell resistance to photokilling and/or provide surviving cells with a growth and migratory advantage.…”

“…A less common intervention for solid tumors is photodynamic therapy (PDT), which employs non-ionizing radiation. PDT was introduced about 45 years ago as a minimally invasive modality involving a photosensitizing agent (PS), PS-exciting visible-to-near infrared light, and molecular oxygen (12)(13)(14). All three components (PS, light and O 2 ) must be engaged concurrently for PDT to lethally damage tumor cells, which often occurs via formation of the cytotoxic ROS, singlet oxygen ( 1 O 2 ).…”

“…Another advantage of PDT is site-specificity, i.e. limitation of photodynamic action to the tumor site at which light is directed, typically via fiber optic transmitters (13,14). An oligomeric hematoporphyrin preparation, now known as Photofrin ® , was the first PS to receive FDA approval for PDT ca.…”

“…An oligomeric hematoporphyrin preparation, now known as Photofrin ® , was the first PS to receive FDA approval for PDT ca. 20 years ago, and it is now used for a variety of solid tumors (13,14). 5-Aminolevulinic acid (ALA)-based PDT is a more recently developed alternate in which ALA (or an ALA ester) is administered as a pro-PS.…”