Photodynamic Therapy

Abstract

Photodynamic therapy involves administration of a tumor-localizing photosensitizing agent, which may require metabolic synthesis (i.e., a prodrug), followed by activation of the agent by light of a specific wavelength. This therapy results in a sequence of photochemical and photobiologic processes that cause irreversible photodamage to tumor tissues. Results from preclinical and clinical studies conducted worldwide over a 25-year period have established photodynamic therapy as a useful treatment approach for some cancers. Since 1993, regulatory approval for photodynamic therapy involving use of a partially purified, commercially available hematoporphyrin derivative compound (Photofrin) in patients with early and advanced stage cancer of the lung, digestive tract, and genitourinary tract has been obtained in Canada, The Netherlands, France, Germany, Japan, and the United States. We have attempted to conduct and present a comprehensive review of this rapidly expanding field. Mechanisms of subcellular and tumor localization of photosensitizing agents, as well as of molecular, cellular, and tumor responses associated with photodynamic therapy, are discussed. Technical issues regarding light dosimetry are also considered.

Photophysical properties and intracellular imaging of water-soluble porphyrin dimers for two-photon excited photodynamic therapy

“…Photodynamic therapy (PDT) is a light-activated treatment which is 25 used in the clinic to destroy diseased tissues, 1,2 and is in trials for the eradication of localised bacterial infections. 3 PDT drugs (or photosensitisers) achieve their therapeutic effect by generating a cytotoxic species in the presence of light, by either electron-transfer (Type I) or energy-transfer (Type II) processes.…”

Involvement of retinoblastoma (Rb) and E2F transcription factors during photodynamic therapy of human epidermoid carcinoma cells A431

“…The treatment is based on a selective uptake of porphyrinbased photosensitizing chemical in tumor tissue relative to the surrounding normal tissue followed by irradiation of the tumor with light (visible or near infra-red), typically delivered through a laser. PDT is showing promise against a variety of solid tumors as well as against many non-malignant diseases (Dougherty et al, 1998;Pass, 1993;Tom, 1997;Gomer, 1991). PDT is known to result in a sequence of photochemical and photobiological events that leads to an oxidative damage to many of cellular targets, subsequently resulting in the killing of cancerous cells and thereby tumor ablation that often leads to a complete cure (Dougherty et al, 1998).…”

“…PDT is showing promise against a variety of solid tumors as well as against many non-malignant diseases (Dougherty et al, 1998;Pass, 1993;Tom, 1997;Gomer, 1991). PDT is known to result in a sequence of photochemical and photobiological events that leads to an oxidative damage to many of cellular targets, subsequently resulting in the killing of cancerous cells and thereby tumor ablation that often leads to a complete cure (Dougherty et al, 1998). The mechanism(s) of the PDT-mediated cell killing that results in tumor ablation is not fully understood.…”

“…Research aimed at de®ning the mechanism(s) of biological e ects of PDT has demonstrated the involvement of singlet oxygen and possibly other reactive oxygen species as a pre-requisite for PDTe ect (Dougherty et al, 1998). Studies have also suggested the involvement of certain early response genes such as c-fos, c-jun, c-myc, egr-1 (Luna et al, 1994), heat shock protein HSP-70 (Gomer et al, 1996) and nuclear factor kappa B (NFkB) as PDT-response (Ryter and Gomer, 1993).…”

Chemical modification of temoporfin – a second generation photosensitizer activated using upconverting nanoparticles for singlet oxygen generation

“…[1][2][3] Individually, these components are harmless; however, when combined, a putative cytotoxic agent, singlet oxygen ( 1 O 2 ), is generated. It is the 1 D g form of singlet oxygen that induces oxidation damages on cell components, resulting in cytotoxic reactions in the cells via necrosis or apoptosis, the self-destruction mechanisms of cells.…”