The antioxidant ability of thiol compounds has been the subject of much of the current research about oxidative stress. The direct scavenging of hydroxyl radicals by thiols has been suggested as their protection mechanisms. Nevertheless, the interaction of thiols with reactive radicals can generate thiyl radicals, which, in turn, may impart a pro-oxidant function. The purpose of this study has been to establish the effect of the thiol compounds N-acetyl-L-cysteine (NAC) and glutathione (GSH) against the peroxidative processes involving membrane lipids. The results obtained support the ability of NAC and GSH to suppress the 2,2 0 -azobis-(2-amidinopropane) dihydrochloride (AAPH)-dependent or to enhance the Fe 2+ /H 2 O 2 -dependent oxidative actions. The evaluation of thiobarbituric acid reactive substances (TBARS) production, the study of the influence of oxidants on membrane fluidity and the measurements of the changes in the fluorescence of bilayer probes, such as 3-( p-(6-phenyl)-1,3,5-hexatrienyl)phenylpropionic acid (DPH-PA), have shown the antioxidant and pro-oxidant effects of both NAC and GSH. Also their dependence on the nature of the radicals generated by the oxidative systems used has been shown. The use of ESR spectroscopy has allowed us to establish the ability of these compounds to scavenge the AAPH-derived radicals, to determine the formation of thiyl radicals in the iron-mediated oxidation and to evaluate the enhanced production of hydroxyl radicals by NAC and GSH.

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Photodynamic therapy (PDT) requires photosensitizer, light, and oxygen to induce cell death. The majority of efforts to advance PDT focus only on the first two components. Here, we employ perfluorocarbon nanoemulsions to simultaneously deliver oxygen and photosensitizer. We find that the implementation of fluorous soluble photosensitizers enhances the efficacy of PDT. Phototherapeutics are emerging avenues to mitigate side-effects of treatments due to the spatiotemporal control that can be achieved with light. 1 Photodynamic therapy (PDT), a classic phototherapeutic, employs a photosensitizer to generate reactive oxygen species (ROS) that induce local cell death (Figure 1A). 1 Current clinical uses of PDT include treatment of actinic keratosis, small cell carcinoma, pleural mesothelioma, oesophageal, non-small cell lung and skin cancer with other applications on the horizon as new photosensitizers and endoscopic technologies are developed. 2 Photosensitizer optimization and expanding the scope of tissue that can be irradiated with light contribute to the majority of advancements in PDT. 3 These are critical components; however, the direct therapeutic effect of PDT is a result of ROS such as singlet oxygen (1 O 2). 4 Hypoxia is a hallmark of many tumors 5 and limits the amount of ROS that can be generated even if ample light and photosensitizer are present. The ideal therapeutic for PDT is one that simultaneously delivers oxygen and photosensitizer to the disease site. Perfluorocarbon (PFC) nanoemulsions, droplets of fluorous solvent stabilized by a surfactant, are a compelling platform for PDT owing to the high oxygen content in perfluorocarbons (Figure 1B). 6 Previously, we have shown that fluorophores can be localized inside PFC nanoemulsions when fluorous chains are appended to the chromophore scaffold. 7 We imagined that a similar strategy could be employed to load PFC nanoemulsions with a photosensitizer to result in an exceptional nanomaterial for PDT (Figure 1C). Efforts to enhance PDT with perfluorocarbons began in 1988 when Henderson and co-workers co-injected a porphyrin photosensitizer with PFC nanoemulsions. 8 Despite promising results, this approach remained dormant for 25 years until cyanine dyes were embedded into the surfactant layer of PFC nanoemulsions to facilitate dual oxygen and photosensitizer delivery. 9 Contemporary variants of co-administration of photosensitizer and PFC nanoemulsions have also been pursued. 10 Figure 1. (A) Photodynamic therapy (PDT) involves the introduction of a photosensitizer which generates reactive oxygen species (ROS) upon irradiation with light to result in cell death. (B) Perfluorocarbon (PFC) nanoemulsions are droplets of fluorous solvent stabilized with surfactant. They have high oxygen content. (C) One step formulation of PFC nanoemulsions for PDT. Collectively, these reports demonstrate the potential of PFC nanoemulsions for PDT. However, organic photosensitizers are not compatible with the fluorous solvent, which can lead to inefficient photosensitization ...

Background: Photodynamic therapy (PDT) is a non-invasive and innovative cancer therapy based on the photodynamic effect. In this study, we sought to determine the singlet oxygen production, intracellular uptake, and in vitro photodynamic therapy potential of Cetixumab-targeted, zinc(II) 2,3,9,10,16,17,23,24-octa(tert-butylphenoxy))phthalocyaninato(2-)-N29,N30,N31,N32 (ZnPcOBP)-loaded mesoporous silica nanoparticles against pancreatic cancer cells. Results: The quantum yield (ΦΔ) value of ZnPcOBP was found to be 0.60 in toluene. In vitro cellular studies were performed to determine the dark- and phototoxicity of samples with various concentrations of ZnPcOBP by using pancreatic cells (AsPC-1, PANC-1 and MIA PaCa-2) and 20, 30, and 40 J/cm2 light fluences. No dark toxicity was observed for any sample in any cell line. ZnPcOBP alone showed a modest photodynamic activity. However, when incorporated in silica nanoparticles, it showed a relatively high phototoxic effect, which was further enhanced by Cetuximab, a monoclonal antibody that targets the Epidermal Growth Factor Receptor (EGFR). The cell-line dependent photokilling observed correlates well with EGFR expression levels in these cells. Conclusions: Imidazole-capped Cetuximab-targeted mesoporous silica nanoparticles are excellent vehicles for the selective delivery of ZnPcOBP to pancreatic cancer cells expressing the EGFR receptor. The novel nanosystem appears to be a suitable agent for photodynamic therapy of pancreatic tumors.