RE:RE:Not photodynamic therapyAlso Drs. McFarland, Lilge and colleaguea went into some detail about the mechanism of PS activation in their 2019 paper:
Transition Metal Complexes and Photodynamic Therapy from a Tumor-Centered Approach: Challenges, Opportunities, and Highlights from the Development of TLD1433 "The mechanisms of the photodynamic effect (and hence PDT) are inherently complex, but they generally fall into one of two categories: type I and type II photoprocesses..... However, the explosion of multidisciplinary research related to PDT has generated the haphazard, and often incorrect, use of such terms, but there have been attempts to set matters straight by defining the “ten tips for type I and type II photosensitized oxidation reactions”. Both Type I and Type II mechanisms have an absolute dependence on molecular oxygen (Scheme 1): Type II mostly involves energy transfer from the photosensitizer to ground-state to yield singlet oxygen (1O2), and type I involves photoinduced electron transfer that leads to the formation of superoxide (O2•-) or hydroperoxyl radicals (HO2•). Cadet and Greer emphasized that “photodynamic action is killing via Type I or Type II” photoprocesses and that the term “oxygen-independent photodynamic action should not be used”. Both Type I and Type II photosensitized reactions result in biomolecule degradation and ultimately tissue damage/destruction.
Even when considering the contribution of only these two photosensitization pathways, the distinction cannot be made easily, and they can be expected to occur together. The distinguishing tests (e.g., lifetime in deuterated solvent, azide quenching, radical spin-trapping) do not reliably discriminate between1O2, and O2,•- intermediates. Moreover, the detection of a minute quantity of a given species is not proof of the dominant mechanistic pathway. Lastly, such experiments are performed outside of a biological environment, which further complicates the interpretation of the actual operative mechanism(s) in vitro or in vivo, where it is difficult to obtain convincing mechanistic evidence.
In vitro and in vivo PDT effects likely arise from damage to numerous biological targets through multiple mechanistic pathways that change with tissue type, oxygenation status, and PDT regimen. While cell-free mechanistic experiments can reveal some useful information, the results cannot necessarily be extended to cellular environments or whole organisms, where absorption, distribution, metabolism, and excretion (ADME) (as it relates to the photosensitizer) and dosimetry (as it relates to the photosensitizer, light, and oxygen) become influential factors. Nevertheless, the consensus appears to be that the predominant PDT mechanism is Type II and that 1O2 targets unsaturated lipids and certain amino acid side chains as well as the nitrogenous bases of nucleic acids. Herein, we define PDT as the use of a photosensitizer, light (usually visible), and oxygen to generate cytotoxic reactive oxygen species (ROS). These three components of oncologic PDT are harmless individually, but they combine to destroy tumors, occlude tumor vasculature, and invoke an immune response in a two-stage procedure that consists of administration of the photosensitizer, followed by exposure of the affected tissue to light."
DJDawg wrote:
Eog. I have a science question as I don't understand all the nuances of PDT. When light activates a Ru compound such as ruvidar or rutherrin is the light part of the energy transfer process leading to ROS and cell damage or is it more that the compounds are like coiled springs, ready to help generate ROS with the right trigger event? I ask only because the metformin activation makes you think more about the coiled spring analogy whereas I used to visualize the light or xray conveying energy to the molecule and then that leading to changes and then ROS. Metformin doesn't have any energy in it so it would have to be all on teh Ru compound side?