The Microenvironment Effect on the Generation of Reactive Oxygen Species by Pd−Bacteriopheophorbide

Abstract

Generation of reactive oxygen species (ROS) is the hallmark of important biological processes and photodynamic therapy (PDT), where ROS production results from in situ illumination of certain dyes. Here we test the hypothesis that the yield, fate, and efficacy of the species evolved highly depend on the dye's environment. We show that Pd-bacteriopheophorbide (Pd-Bpheid), a useful reagent for vascular targeted PDT (VTP) of solid tumors, which has recently entered into phase II clinical trials under the code name WST09 (trade name TOOKAD), forms appreciable amounts of hydroxyl radicals, superoxide radicals, and probably hydrogen peroxide in aqueous medium but not in organic solvents where singlet oxygen almost exclusively forms. Evidence is provided by pico- and nanosecond time-resolved spectroscopies, ESR spectroscopy with spin-traps, time-resolved singlet oxygen phosphorescence, and chemical product analysis. The quantum yield for singlet oxygen formation falls from approximately 1 in organic solvents to approximately 0.5 in membrane-like systems (micelles or liposomes), where superoxide and hydroxyl radicals form at a minimal quantum yield of 0.1%. Analysis of photochemical products suggests that the formation of oxygen radicals involves both electron and proton transfer from (3)Pd-Bpheid at the membrane/water interface to a colliding oxygen molecule, consequently forming superoxide, then hydrogen peroxide, and finally hydroxyl radicals, with no need for metal catalysis. The ability of bacteriochlorophyll (Bchl) derivatives to form such radicals upon excitation at the near infrared (NIR) domain opens new avenues in PDT and research of redox regulation in animals and plants.

Reversible Photochemical Control of Singlet Oxygen Generation Using Diarylethene Photochromic Switches

“…4 Several approaches for controlling generation and deactivation of 1 O 2 have been reported, e.g., through environmental changes (including solvent or pH), 5 programming with enzymes or DNA, 6 or applying nanomaterials, e.g., carbon nanotubes and quantum dots. 7 These systems provide for either On/Off or high/low functionality to the sensitizers toward generation of 1 O 2 , which can minimize side effects under prolonged exposure to light.…”

Manipulation of redox signaling in mammalian cells enabled by controlled photogeneration of reactive oxygen species

“…This compound and other bacteriochlorophyll-based molecules have been used for generation of cytotoxic levels of ROS in photodynamic therapy (PDT) of different malignancies Preise et al, 2003;Schreiber et al, 2002;Zilberstein et al, 2001) and for modeling superoxide dismutase activity (Ashur et al, 2003). The ROS profile generated by each sensitizer has been determined using electron spin resonance (ESR)-based analyses, time resolved optical spectroscopy and photochemical products analyses under cell-free conditions (Vakrat et al, 1999;Vakrat-Haglili et al, 2002;Vakrat-Haglili et al, 2005) and have been shown to include O 2 -, OH˙and singlet oxygen. The specific ROS generated are highly dependent on the microenvironment in which the photosensitization takes place and are thus expected to induce distinct effects on cellular components situated in each environment.…”

“…The specific ROS generated are highly dependent on the microenvironment in which the photosensitization takes place and are thus expected to induce distinct effects on cellular components situated in each environment. Pd-bacteriochlorophyll derivatives have been shown to largely generate protonated superoxide in lipophilic environments, while generating superoxide and hydroxyl radicals at the lipid/water interface (Vakrat-Haglili et al, 2005). Similarly, because of the innate variance in the half-life of each species (nanoseconds for hydroxyl radical and seconds for superoxide) and the consequential radius of activity (Angstrom and micrometer, respectively), the distance at which the affected molecule is situated will also determine the nature of the response.…”

Intraperitoneal photodynamic therapy mediated by a fullerene in a mouse model of abdominal dissemination of colon adenocarcinoma

“…There exists evidence that aggregated photosensitizers are more likely to carry out type 1 photochemistry compared with perfectly soluble monomeric forms (28). Another possibility is that different reactions can take place at membrane interfaces (29). It is also at present unclear where the electron comes from in reaction 2 when the photosensitization takes place with the probes in aqueous solution.…”