Basic and Clinical Aspects of Photodynamic Therapy

Abstract

Photodynamic therapy (PDT) was originally developed for the treatment of solid tumors by the concerted action of a tumor-localizing agent, named as the photosensitizer, molecular oxygen and visible light source. The photoinduced cytotxic species are mainly represented by singlet oxygen ( 1 O 2 ), even though the formation of NO has been observed in selected situations. Optimal results are generally obtained by using porphyrins and their tetrapyrrolic analogues as the photodynamic agents, since these compounds display an intense absorbance of the red spectra wavelengths, which are endowed with a particularly deep penetration into most biological tissues. While several porphyrins exhibit an intrinsic preferential affinity for malignant tissues, the selectivity of the tumor localization can be significantly enhanced by pre-binding the photosensitizer with a targeting agent, such as an antibody or a vehicle (e.g., glycoproteins, peptides, oligonucleotide aptamers, growth factors, lipoproteins) directed against antigens or receptors which are specifically present at the surface of tumor cells. Recently, novel perspectives have been opened by the association of the photosensitizer with nanoparticles, which can be made to be multifunctional, thereby allowing the simultaneous delivery of photoactivatable moieties acting by different mechanisms, as well as of phototherapeutic and photodiagnostic agents. The chemical structure of the photosensitizer and the nature of the possible carrier have important consequences with regards to the distribution of the photosensitizer among different compartments of the tumor tissue, such as neoplastic cells, blood vessels or the non-vascular stroma, as well as its localization in different subcellular sites; these would obviously affect the mechanism of photoinduced tumor damage, modulating the competition between necrosis, apoptosis and autophagia, the importance of photoinduced hypoxia, and the balance between enhancement of the immune response and immunosuppression. So far, about 250 randomized clinical trials have been officially reported for 4 V. Rapozzi and G. Jori PDT of tumors, and essentially all types of solid tumors with the exception of melanotic melanoma have been found to be positively responsive to the photodynamic treatment. Thus, PDT is currently considered as a reasonable option for the treatment of a variety of malignant lesions for curative or palliative purposes by using either external or endoscopic irradiation approaches via non-coherent or laser light sources.

A study of concentration changes of Protoporphyrin IX and Coproporphyrin III in mixed samples mimicking conditions inside cancer cells for Photodynamic Therapy

“…Since the 1980s studied extensively for different types of tumors. Up to 5.000 publications concerning PDT and about 250 officially reported clinical trials have been generated [1]. Although a positive response and good reproducibility was observed for nearly all types of solid tumors and PDT has been accepted as a treatment in various skin cancers, it is still in a niche within clinical practice for the treatment of cancers.…”

“…If the treatment starts too early or too late, a sufficiently high concentration of PPIX, to produce ROS in strategic locations inside the cell, cannot be ensured. This interval of time between the ALA inoculation and the light delivery is known as “drug-light interval” and is one of the main factors influencing the outcome of a PDT procedure [1]. Nowadays the time for the drug-light interval generally used in clinical applications has been taken following the literature, where the interval has been adjusted for each patient equally [6].…”

Near-Infrared-Triggered Photodynamic Therapy toward Breast Cancer Cells Using Dendrimer-Functionalized Upconversion Nanoparticles

“…PDT based on the photochemical reactions of photosensitizers (PSs) is a treatment strategy involving light irradiation at appropriate wavelengths, by which PS molecules can produce cytotoxic reactive oxygen species (ROS) and singlet oxygen ( 1 O 2 ) to destroy nearby cancer cells [ 15 ]. The greatest advantage of PDT is the ability to selectively treat tumor cells by using light under spatiotemporal control.…”

Expression of β-Catenin, E-Cadherin, and α-Smooth Muscle Actin in Basal Cell Carcinoma Before Photodynamic Therapy in Non-recurrent and Recurrent Tumors: Exploring the Ability of Predicting Photodynamic Therapy Outcome

“…Additionally, exploration of other potential markers for predicting PDT outcome would be interesting as it is possible that mechanisms outside tumor invasiveness or aggressiveness may be related to PDT response. 38 In conclusion, the results show that E-cadherin expression is increased in BCCs recurring after PDT, as well as increased expression of β-catenin in the stroma and lower tumor edge, suggesting they could be potential predictive markers for PDT outcome. Further studies are necessary to investigate whether these results are of clinical value.…”