Elaboration and characterization of new porphyrin patterned superparamagnetic nanoparticles for application in photodynamic therapy of cancer

Current chemotherapy regimens for cancer treatment most often use highly toxic molecules that lead to serious adverse reactions in patients. Photodynamic therapy, a method based on the administration of an active molecule (photosensitizer) followed by light irradiation, limits these side effects. To improve the efficiency of photosensitizers, we have developed porphyrin-patterned superparamagnetic nanoparticles. Indeed, nanoparticles easily enter cancer cells by a mechanism of passive endocytosis. This process circumvents the problems of multidrug resistance acquired by cancer cells. Such magnetic nanoparticles carrying a photosensitive drug should help develop molecular platforms endowed with dual efficiency by combining the lethal effect of photocytotoxic drugs (PDT) with the magnetic properties of the carrier (thermotherapy). To this end, iron oxide nanoparticles were synthesized and stabilized in aqueous medium by a modified dextran. Then, Click Chemistry reactions were used to decorate these nanoparticles with hydrosoluble porphyrins (glucosylated, sulfonated and cationic pyridinium ions). The synthesized compounds were characterized by various spectroscopic (UV-visible, fluorescence, IR, mass, ¹H NMR) and physicochemical (Mass, TEM, magnetometry, ATG) methods. In a second step, these nanoparticles were attached to polyamines (polyethylenimine 600) by Click Chemistry reactions, to enhance their cellular internalization. The first in vitro tests performed on a human keratinocyte cell line (HaCaT cells) demonstrated the photocytotoxic activity of these compounds; more specifically, PEI-cationic porphyrins nanoparticles were found to be twenty times more efficient than Photofrin^R. (author)