A dinuclear ruthenium(II) complex excited by near-infrared light through two-photon absorption induces phototoxicity deep within hypoxic regions of melanoma cancer spheroids

The dinuclear photo-oxidizing RuII complex [{Ru(TAP2)}2(tpphz)]4+ (TAP = 1,4,5,8- tetraazaphenanthrene, tpphz = tetrapyrido[3,2-a:2',3'-c:3'',2''- h:2''',3'''-j]phenazine), 14+ is readily taken up by live cells localizing in mitochondria and nuclei. In this study, the two-photon absorption cross-section of 14+ is quantified and its use as a two-photon absorbing phototherapeutic is reported. It was con-firmed that the complex is readily photo-excited using near infrared, NIR, light through two-photon absorption, TPA. In 2-D cell cul-tures, irradiation with NIR light at low power results in precisely focused photo-toxicity effects in which human melanoma cells were killed after 5 minutes of light exposure. Similar experiments were then carried out in human cancer spheroidsthat provide a realistic tumor model for the development of therapeutics and phototherapeutics. Using the characteristic emission of the complex as a probe, its up-take into 280 µm spheroids was investigated and confirmed that the spheroid takes up the complex. Notably TPA excitation results in more intense luminescence being observed throughout the depth of the spheroids, although emission intensity still drops off toward the necrotic core. As 14+ can directly photo-oxidize DNA without the mediation of singlet oxygen or other reactive oxygen species, photo-toxicity within the deeper, hypoxic layers of the spheroids was also investigated. To quantify the penetration of these phototoxic effects, 14+ was photo-excited through TPA at a power of 60 mW, which was progressively focused in 10 µm steps throughout the entire z-axis of individual spheroids. These experiments revealed that, in irradiated spheroids treated with 14+, acute and rapid photo-induced cell death was observed throughout their depth, including the hypoxic region

Improvement of sputtered oxide coating adherence and integrity for turbine airfoil applications. Combustion zone durability program. Task III: dense surface sputtered ceramic coatings. Annual technical progress report, October 1, 1978-September 30, 1979

Two aspects of the durability of modified ZrO/sub 2/ ceramic thermal barrier coatings for gas turbine airfoils are being investigated in this program. First, adherence of coatings of these materials has historically been difficult to achieve due to mismatch in thermal expansion coefficients and other properties between ceramic coatings and metallic substrates. Second, if the ceramic coatings are discontinuous, as for many plasma sprayed coatings, then condensate from the combustion environment may permeate the coating and volume changes in this condensate during subsequent service cycles may produce coating spallation. The adherence problem was approached by seeking to sputter deposit ceramic coatings over either sputter-etched, closely spaced, high aspect ratio substrate surface cones or by sputter depositing ceramic coatings over sputtered CoCrAlY coatings containing a very high density of columnar voids (leaders). The objective in both instances was to provide a compliant fibrous metal attachment between metal substrate and ceramic coating to absorb property mismatches. The permeability problem was approached both by coating a segmented (fibrous columnar) ceramic layer with a continuous and impervious metal sealing layer that is not required to provide structural strength or insulation, and by coating the segmented ceramic layer with a continuous layer of the same ceramic material

Universitaet Koblenz-Landau, Institut fuer Informatik. Technical reports -21/97-25/97

SIGLEAvailable from TIB Hannover: RO 6844(1997,21/25) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekDEGerman