| Since first used about a hundred years ago, photodynamic therapy is now a well-established treatment for a variety of cancers and other diseases, and is emerging as new treatments for a broad range of other cancers, antibiotics, and antivirals. In terms of cancer therapy, a dye capable of photosensitizing the formation of singlet oxygen and/or producing reactive oxygen species is delivered to the cancer tissues. Upon activation by either a band or a specific wavelength of light, the reactive oxygen species produced will oxidize nearby biomolecules such as aromatic amino acids, double bonds in lipids, and nucleic acid with diffusion limited kinetics. The resulting oxidative stress induces necrosis or apoptosis depending on a variety of factors including degree and location of the damage. Currently, about four drugs are approved to treat several different types of cancer, these are porphyrinoids or porphyrin precursors, but none have cancer cell targeting motifs appended to the dye.;To improve the photodynamic therapy efficacy, significant research is focused on development of new photosensitizers that may have advantages over the ones currently used. Major research thrusts include: (A) improving dye light absorption in the 650 nm--850 nm region for activation deeper into tissues and tumors, (B) improve selectivity towards cancer cells, and (C) faster biodistribution and clearance from the body after treatments. Together with these objectives, it is also important to understand the mechanism of action in terms of how the photogenerated toxic species initiate the different pathways for cell death. This latter information is important for the design and development of new compounds, and to understand how the cancer cells respond to this method of treatment.;Our lab developed a series of glycosylated porphyrins using a thioether linkage. The thioglycosylated phorphyrins are nonhydrolysable under physiological conditions and have been shown to be active photodynamic therapeutics, but only weakly absorb light above 650 nm. The chlorin, bacteriochlorin, and isobacteriochlorin derivatives are presented as new photodynamic therapy and dual-function imaging/therapeutic agents with photophysical properties that afford significant advantages over the parent compound, both in terms of light activation and imaging. The effectiveness of photodynamic treatment in initiating necrosis and apoptosis are analyzed and described. In addition, the isobacteriochlorin is presented as a two photon active compound, wherein it is activated by two photons between 780 nm and 880 nm. The two photon absorption property of the isobacteriochlorin is an important feature that allows optimal wavelengths to be used and is part of a burgeoning field in photodynamic therapy. Considering the different photophysical properties of this compound, the possibility to use this compound as a dual function bioimaging/therapeutic agent is discussed. |
