PH-controlled solubilization of photosensitizer tetraphenylporphyrin

Abstract

pH-controlled solubilization technique for hydrophobic porphyrin photosensitizers, which tetrapyrrole platform is a pH-dependent anion-molecular receptor, using anionic amphiphilic nanoparticles is proposed. Water-soluble forms of tetraphenylporphyrin were made as the complexes with sodium dodecyl sulfate micelles H2P(Ph)4/(NaDS)64 and with nanoparticles of biocompatible polysulfonate Nafion DE 1020 H2P(Ph)4/NNP. Diprotonation of these complexes leads to the fluorescence enhancement in the “therapeutic window” spectral region, and the integral intensity exceeds the value for the PDT drug Fotoditazin®. A unique feature of the excited complex H2P(Ph)4/NNP is the shift of its protonation equilibrium to the physiological pH value of healthy tissues. This pH value is the starting point of pH-induced H2P(Ph)4/NNP fluorescence increasing. In the pH range, corresponds to the acidic tumors microenvironment, integral fluorescence of H4P2+(Ph)4/NNP increases to 250%, which is quarter of the maximum fluorescence value. These results demonstrate the possibility and the concept of pH-dependent “off-on” photosensitizers for photodynamic theranostics based on H2P(Ph)4 derivatives, with low fluorescence and phototoxicity in normal tissues and high fluorescence and phototoxicity inside the tumor microenvironment.