Abstract
The overproduction of hydrogen peroxide is an inherent feature of some tumour cells and inflamed tissues. We took advantage of this peculiarity to eliminate cells using chemiluminescent peroxyoxalate reaction. We designed dispersions containing polyoxalate and tetramethylhematoporhyrin (TMHP) in dimethylphthalate droplets stabilized with Pluronic L64. The porphyrin plays the dual role. On the one hand, it serves as an activator of the peroxyoxalate reaction of polyoxalate with intracellular hydrogen peroxide and experiences excitation as a result of the reaction. The light emitted in the reaction in the model system without cells was used to optimize the dispersion’s composition. On the other hand, TMHP acts as a photosensitizer (PS) causing cell damage. The formation of singlet oxygen led to cell elimination if the dispersions were used in combination with inducers of oxidative stress: hydrogen peroxide, paraquat, antitumour drug doxorubicin, or a nutritional additive menadione. The PS-induced cytotoxicity correlated with the level of intracellular ROS. The developed approach targeted to endogenous ROS is orthogonal to the classical chemotherapy and can be applied to increase its efficiency.
Highlights
Despite significant progress in technical development of PDT, it is not free from limitations
Further we studied the capacity of chemiluminescence dispersions (CLD) to generate singlet oxygen due to peroxyoxalate chemiluminescent (PO-CL) reaction
We suggested that inability of CLD to eliminate cells was due to insufficient concentration of endogenous hydrogen peroxide necessary for PO-CL reaction
Summary
Despite significant progress in technical development of PDT, it is not free from limitations. The reaction proceeds between active derivatives of oxalic acid and hydrogen peroxide (Fig. 1a). In this work the exogeneous hydrogen peroxide was used to trigger the chemiluminescent reaction. Large amounts of endogenous peroxide are often found in malignant cells and inflamed tissues[13,14,15]. This peculiarity provides the possibility to run PO-CL reaction without addition of exogeneous peroxide and provoked a number of approaches to visualization and elimination of cells with increased ROS production. The emitted chemiluminescence was absorbed by the PS attached to the transferrin molecule inducing selective elimination of cells with elevated amounts of transferrin receptors. Peroxyoxalate chemiluminescent systems combined with the effect of aggregation-enhanced fluorescence[18] and semiconducting polymers[19] were applied for detection of hydrogen peroxide associated with lipopolysaccharide-induced inflammation
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