Research of Yao Liu
Antibacterial photodynamic therapy
Recent research activities are centered on Antibacterial photodynamic therapy (APDT). APDT is a promising approach to treat bacterial infections that are recalcitrant to antibiotics. APDT is based on the photosensitization of bacteria with exogenous compounds referred to as photosensitizers (PS). Cell death is subsequently triggered by lethal oxidative stress induced by irradiation of the infected area with light of a resonant wavelength, typically in the visible wavelength range (400-700 nm). The irradiated ground state PS, located in the bacteria or at the bacterial surface, absorbs the light and is excited to its singlet state (1PS). The excited state electrons undergo intersystem crossing to a lower-energy but longer-lived triplet state (3PS), from which reactive oxygen species (ROS) or reactive molecular transients are generated. The photochemical reactions proceed via a type I or type II mechanism and require close proximity between the 3PS and substrate. Type I reactions generate radicals following triplet state electron transfer from the 3PS to a substrate. A common terminal substrate for type I reactions is molecular oxygen, leading to the production of superoxide anion (O2•‒). In a biological environment, O2•‒ is relatively innocuous but can give rise to more cytotoxic ROS such as hydroxyl radicals (•OH) and carbonate radical anions (CO3•‒) that oxidize biomolecules and cause cell damage and ultimately death. In type II reactions, the excited PS reacts directly with molecular oxygen (O2) and forms the highly reactive singlet oxygen (1O2) via 3PS→O2 energy transfer. Type I and type II reactions are believed to occur simultaneously during APDT and the ratio of the occurrence between the two is dependent on the type of PS that is administered and the microenvironment in which APDT is applied. Together with my collaborators we strive to identify novel photosensitizers and optimize delivery systems for specific targeting to apply in pathogenic bacterial strains, both Gram-positive and Gram-negative.