Tuning the formation of reactive oxygen species mediated by exogenous photosensitizers for efficient photodynamic therapy of cancer and bacterial infections
Abstract
Interaction of partially reduced oxygen products and singlet excited molecular oxygen (singlet oxygen), commonly termed reactive oxygen species (ROS), with key cellular constituents, could lead to disfunction of the cells and ultimately their death. Even though such processes are believed to be responsible for ageing and certain diseases, controlled formation of ROS in pathological tissues might be exploited as alternative treatment for cancer and bacterial infections. This treatment, called photodynamic therapy (PDT) and antibacterial photodynamic inactivation (APDI), is based on localized generation of ROS using appropriate photosensitizing dyes, molecular oxygen and active light. Although singlet oxygen is generally viewed as a key species responsible for photodynamic oxidative damage, its photogeneration requires relatively high oxygenation of the treated tissue. At low concentration of oxygen, Type I photochemistry prevails with the dominant role of free radicals. This paper will discuss the mechanisms of significant potentiation of photodynamic inactivation of both gram-positive and gram-negative bacteria by a wide range of different inorganic salts, which contributed to the formation of different oxidizing radicals. The preferential Type I or Type II photochemistry in photodynamic killing of in vitro cancer cells using Pd-substituted bacteriochlorophyll derivatives or functionalized fullerenes and surface-modified TiO2 nanoparticles will be also briefly reviewed. The reviewed collaborative studies were caried out employing standard cell and molecular biology techniques and selected physicochemical techniques such as laser flash photolysis, singlet oxygen phosphorescence, EPR-spin trapping and EPRoximetry, and detection of lipid hydroperoxides by HPLC-EC(Hg) using cholesterol as a reporter molecule. Although the exact role of free radicals and singlet oxygen in cancer and antibacterial PDT remains difficult to be unambiguously determined, tunning the specific formation of ROS may be utilized to optimize the efficiency of the treatment.
