Strategies for Enhanced Photodynamic Therapy Effects^†

Abstract

Photodynamic therapy (PDT) is a treatment modality for the selective destruction of cancerous and nonneoplastic pathologies that involves the simultaneous presence of light, oxygen and a light-activatable chemical called a photosensitizer (PS) to achieve a cytotoxic effect. The photophysics and mechanisms of cell killing by PDT have been extensively studied in recent years, and PDT has received regulatory approval for the treatment of a number of diseases worldwide. As the application of this treatment modality expands with regard to both anatomical sites and disease stages, it will be important to develop strategies for enhancing PDT outcomes. This article focuses on two broad approaches for PDT enhancement: (1) mechanism-based combination treatments in which PDT and a second modality can be designed to either increase the susceptibility of tumor cells to PDT or nullify the treatment outcome-mitigating molecular responses triggered by PDT of tumors, and (2) the more recent approaches of PS targeting, either by specific cellular function-sensitive linkages or via conjugation to macromolecules.

New Halogenated Water‐Soluble Chlorin and Bacteriochlorin as Photostable PDT Sensitizers: Synthesis, Spectroscopy, Photophysics, and in vitro Photosensitizing Efficacy

“…[31] In spite of the remarkable progress in PDT, the need for more efficient photosensitizers that are chemically pure, less phototoxic, have better localizing properties, and absorb light more intensely and deeper into the near-infrared, remains unfulfilled. The efficacy of PDT may be enhanced by combined therapies, while the photosensitizer specificity might be improved by various carrier-mediated targeting systems, [32] but the intrinsic photosensitizer properties remain a limiting factor for the widespread use of PDT for the treatment of cancer.…”

One- and two-photon activated phototoxicity of conjugated porphyrin dimers with high two-photon absorption cross sections

“…[1][2][3][4][5][6][7][8] The treatment is relatively benign and gives good cosmetic outcomes. One of the major drawbacks is that the drugs are excited by visible light which cannot penetrate deeply into tissues.…”

Targeting cancer cells by using an antireceptor antibody-photosensitizer fusion protein

“…cancer treatment because of the absence of systemic toxicity of the drug in the absence of light irradiation, the possibility to irradiate the tumor selectively, the opportunity of treating multiple lesions simultaneously, and the ability to retreat a tumor to improve the response (1). Upon light irradiation in an oxygen-rich environment, photosensitizers produce short-lived but highly reactive oxygen species (ROS), such as singlet oxygen 1 O 2 , or radical species, such as OH ⅐ , O 2 ⅐ , which effectively oxidize the cellular components at locations where they have been produced (2).…”