Targeted photosensitizers and controlled singlet oxygen generation for therapeutic applications

Abstract

Photodynamic therapy of cancer plays a pivotal role due to its many superior features and potential. Considering the pathways for improving the practice of PDT of cancer is gradually increasing, enhancing the selectivity of photodynamic action is an obvious choice. Being the source of reactive oxygen species in the body, mitochondrion is one of the most proper organelles to target. There is plethora of findings suggesting that triphenlyphosphonium cation is a very favorable mitochondria targeting agent. Another aspect of PDT requires creation of smart molecules which respond to either the increased temperature or ion concentrations in order to release 1O2. Cyclic endoperoxides of naphthalene and anthracene could help in achieving the desired objective of storing 1O2 and regenerating it again when appropriate conditions meet. The half-life cycloreversion of 1,4-Dimethylnaphthalene could be changed at least 100-fold when 2-position of the naphthalene is sterically hindered. Taking advantage of the fact that fluoride ions’ silicophile nature, a novel perspective for drug design can be proposed. In the final project, a certain level magnetic hyperthermia, large enough to cause endoperoxide cycloreversion, but not large enough to cause necrotic death, is being sought after. Controlled generation singlet oxygen by the application of tissue penetrating alternating magnetic fields is the ultimate goal for that project.