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Interest in Photodynamic Therapy is increasing; however, the translation of new photosensitizers into the clinic is stalled, despite increasing numbers of drugs synthesized for this purpose. One impediment in translating these promising compounds for photodynamic therapy into clinical studies is wide variability in the reporting of in vitro efficacy, not allowing the receptor industry to identify very promising compounds. Here we propose an in vitro cell response model, based on the photodynamic threshold model published previously, to compare the quantum efficiency of different ruthenium coordination-complexes based photosensitizers. The thresholds are given in [hν cm-3] units or the number of photons absorbed by the photosensitizer per volume. Here we compare the efficacy of Ruthenium Coordination complexes published in the past 20 years as model systems for a strategy to provide wavelength and absorption coefficient independent efficacy reports for in vitro PDT studies. Equation (1), Presents a calculation of the threshold value whereby ε(λ) [µM-1 cm-1] presents the wavelength-dependent molar absorption coefficient, [PS] LD50 the photosensitizer concentration when the LD50 is reached for a constant radiant exposure H [J cm-2]. hc/λ is the conversion factor from [J cm-2] to [hν cm-3]. ▪ By calculating a photosensitizer's quantum efficiency to reach a predetermined endpoint, here to induce a 50% reduction in cell survival, the LD50 results in a wavelength and molar extinction coefficient independent measure. Additionally, the threshold value contains the responsivity of a cell line to PDT The available studies comprised reports for ALA-induced PPIX, using PDT activation wavelengths between 450 nm and 700 nm, either a laser wavelength or broadband light sources, applied to different cell lines. For TLD1433 data for ten different cell lines, were available with excitation wavelengths ranging from 525 nm to 625 nm. For ALA induced PPIX mediated PDT in vitro the average photodynamic LD 50 threshold was 5.08 1016 ± 7.04 1016 [hν cm−3] and for TLD1433 9.28 1016 ± 1.08 1017 [hν cm−3]. Threshold values of compounds are in Table. The complete table will be presented during the conference presentation [ABSTRACT FROM AUTHOR]

One major challenge in gene therapy is the host immune responses against viral vectors. Previous studies indicate the involvement of NK cells in stunted gene expression in viral vector mediated gene therapy. To understand the problem of the immune responses, we have developed an in-vitro co-culture system with human NK cell line, macrophages and airway epithelial cells. We showed that small molecule blockers, CAPE and ruxolitinib, for NF-κB and JAK-STAT pathways, respectively, significantly inhibited cytokine secretion by macrophages. When NK cells are co-cultured with helperdependent adenoviral (HD-Ad) vector activated macrophages, IFN-γ cytokine expression by NK cells increased significantly, which was inhibited effectively by ruxolitinib and CAPE, and there was an additive effect when both inhibitors were used. We demonstrated that NK cells activated by cytokines produced by HD-Ad-activated macrophages kill HD-Ad vector transduced bronchial epithelial cells. This cell killing activity was significantly reduced by CAPE and ruxolitinib. Combination of these two inhibitors had an additive effect on inhibiting NK cell mediate killing of gene transduced cells. Transient inhibition of NK cell response at its peak may enhance sustained gene expression. Our data suggest that combination of CAPE and ruxolitinib may help in protecting gene transduced airway epithelial cells to prolong transgene expression. [ABSTRACT FROM AUTHOR]

Ruthenium(II)-based coordination complexes have emerged as photosensitizers (PSs) for photodynamic therapy (PDT) in oncology as well as antimicrobial indications and have great potential. Their modular architectures that integrate multiple ligands can be exploited to tune cellular uptake and subcellular targeting, solubility, light absorption, and other photophysical properties. A wide range of Ru(II) containing compounds have been reported as PSs for PDT or as photochemotherapy (PCT) agents. Many studies employ a common scaffold that is subject to systematic variation in one or two ligands to elucidate the impact of these modifications on the photophysical and photobiological performance. Studies that probe the excited state energies and dynamics within these molecules are of fundamental interest and are used to design next-generation systems. However, a comparison of the PDT efficacy between Ru(II) containing PSs and 1 st or 2 nd generation PSs, already in clinical use or preclinical/clinical studies, is rare. Even comparisons between Ru(II) containing molecular structures are difficult, given the wide range of excitation wavelengths, power densities, and cell lines utilized. Despite this gap, PDT dose metrics quantifying a PS's efficacy are available to perform qualitative comparisons. Such models are independent of excitation wavelength and are based on common outcome parameters, such as the photon density absorbed by the Ru(II) compound to cause 50% cell kill (LD 50 ) based on the previously established threshold model. In this focused photophysical review, we identified all published studies on Ru(II) containing PSs since 2005 that reported the required photophysical, light treatment, and in vitro outcome data to permit the application of the Photodynamic Threshold Model to quantify their potential efficacy. The resulting LD 50 values range from less than 10 13 to above 10 20 [hν cm -3 ], indicating a wide range in PDT efficacy and required optical energy density for ultimate clinical translation.