Gary L. Cantrell

In vitro biological effects of novel type I photosensitizers and their mechanism of action

Photodynamic therapy involving Type 2 photosenstizers has been conspicuously successful in the treatment of various lesions. Type 1 process, in contrast has not received much attention despite its considerable potential. We have prepared several classes of molecules containing fragile bonds that will produce reactive intermediates such as radicals and nitrenes upon photoexcitation with UV-A and visible light. In a primary screen, many of these compounds had a significant concentration and light dose dependent effect on the cell viability on U937. The chemistry of these compounds differentiated their ability to induced cytotoxic effects. To further establish these findings, we tested one compound representing each class of chemistry in three different tumor cell lines. Cells were incubated with three different concentrations (100μM, 25μM and 6.25μM) and exposed to UV light dose of 4J/cm2 and 8J/cm2. The compounds showed varying effects on viability in different cell lines. Finally we also investigated the ability to induce apoptosis as the mechanism of cell death in HCT116 cell lines using the experimental conditions mentioned. The type 1 photosensitizers induced apoptosis as early as 4 hours after exposure in HCT116 cells and the rate of apoptosis increased with time with majority of cells in late apoptotic or necrotic stage.

Ultrasound contrast agents

New ultrasound contrast agents that comprise microbubbles encapsulating a gas within a shell made from a blend of bipolar compounds having mixed carbon chain length. The compounds have hydrophobic groups selected from the group consisting of straight-chained alkyls, alkylethers, alkylthiolethers, alkyldisulfides, polyfluoroalkyls, and polyfluoroalkylethers having a carbon chain length greater than or equal to 16 and less than or equal to 32. The polar groups are connected to the hydrophobic groups by means of a linker. The polar head groups are selected from the group consisting of CO 2 -M + , SO 3 − M + , SO 4 − M + , PO 3 − M + , PO 4 − M + 2 , N(R) 4 + , a pyridinium or substituted pyridinium group, and a zwitterionic group; R is selected from the group consisting of —H, —CH 3 , alkyl, cycloalkyl, substituted cycloalkyls containing one or more heteroatoms, and benzyl and can be the same or different; and Z′ is a nonionic and M is a cation.

Novel visible light activated type 1 photosensitizers

Photodynamic therapy of tumors involving Type 2 photosenstizers has been conspicuously successful, but the Type 1 process, in contrast, has not received much attention despite its considerable potential. Accordingly, several classes of molecules containing fragile bonds such as azido (-N=N=N), azo (-N=N-), and oxaza (-N-O-) functional groups that produce reactive intermediates such as radicals and nitrenes upon photoexcitation with visible light were prepared and tested for cell viability using U397 leukemia cell line. The cells were incubated with the photosensitizer at various concentrations, and were illuminated for 5, 10, and 20 minutes. The results show that all the photosensitizers caused cell death compared to the controls when exposed to both the photosensitizers and light.