PEGylated poly(lactic-co-glycolic acid) nanoparticles doped with molybdenum-iodide nanoclusters as a promising photodynamic therapy agent against ovarian cancer

Abstract

Photodynamic applications requires efficient intracellular uptake of the photosensitizer that can be achieved through the development of nanoscaled delivery system. Herein, we prepared PEGylated poly(lactic-co-glycolic acid) nanoparticles doped with an octahedral molybdenum cluster complex bearing iodine inner ligands and o-carborane carboxylate apical ligands. This complex is a potent red luminophore and singlet oxygen photosensitizer under UV/blue-light irradiation, making it an attractive theranostic tool for photodynamic therapy and emerging modalities such as X-ray-induced photodynamic therapy or boron neutron/proton capture therapy. However, its hydrophobicity hinders its use in biological application and requires its encapsulation in nanocarriers. The nanoparticles, prepared using the solvent displacement method, displayed ideal properties in terms of size and zeta potential as a drug delivery system and exhibited a robust colloidal stability in biological medium, without the need of additional surfactant. The encapsulated complexes conserved their efficient red luminescence and singlet oxygen photosensitizing activity, while being protected from the detrimental hydrolysis process generally observed for this type of complexes in aqueous media. Evaluation of the in vitro biological activity of the nanoparticles against the ovarian cancer cell line SKOV-3 evidenced efficient uptake into the cellular membrane and cytoplasm and intensive phototoxic effect associated with an appreciable therapeutic window, suggesting potential as a photodynamic therapy agent against ovarian cancer.