A recent study has unveiled with unprecedented detail how singlet oxygen molecules diffuse along double strand DNAs, paving the way to more effective nucleic acid-targeting photodynamic therapy (PDT). A research team at Tokyo Tech used a novel photosensitizer and custom-made DNA sequences to shed light on the optimal position to anchor the photosensitizer to achieve the best oxidizing effect. This could help make this type of PDT more lethal to cancer cells.
Nucleic acid-targeting photodynamic therapy (PDT) is a promising type of targeted therapy that is being actively researched. This treatment relies on special photosensitizers, a type of drug that binds at specific locations in a cell's DNA. Once bound, the cells are irradiated at a precise frequency, which in turn causes the photosensitizer to produce reactive oxygen species (ROS) or singlet oxygen (1O2) molecules. These molecules tend to oxidize nearby nucleic acids, damaging the genetic material and ultimately killing the irradiated cell.
Although the overall process may sound straightforward, there are still many hurdles to overcome before this type of PDT is good enough for clinical practice. One of them is that even though type II oxidation (the one caused by 1O2) has certain advantages over type I oxidation (the one caused by ROS), there is very little information on how far 1O2 molecules can reach once generated. Because of this knowledge gap, it is difficult to decide which location in the DNA should be targeted to achieve the best effect.