Functional titanium dioxide nanoparticle conjugated with phthalocyanine and folic acid as a promising photosensitizer for targeted photodynamic therapy in vitro and in vivo.

Photodynamic therapy (PDT) is a promising cancer treatment that can be implemented using various agents. The conventional photosensitizer Al (III) phthalocyanine chloride tetrasulfonic acid (Pc) has limitations of selectivity in tumor targeting, low affinity to cancer cells, and low two-photon absorption. This study presents a novel photosensitizer FA-TiO-Pc, which has the TiO nanoparticle conjugated with a tumor targeting agent of folic acid (FA), and Pc. FA-TiO-Pc possessed high targeted photodynamic therapeutic activity and excellent biocompatibility. This promising photosensitizer showed high therapeutic drug efficiency in vitro at a low concentration dose and short incubation time under one-photon excitation (OPE). In vivo, when treated with a low dose of FA-TiO-Pc and low light irradiation, the tumor growth was depressed in mice bearing HeLa xenograft tumors with minimal side effects. In addition, the two-photon absorption of FA-TiO-Pc was also enhanced compared to Pc, proving that FA-TiO-Pc system has a great potential to be used for the therapy of the folate receptor positive cancer cells in both OPE-PDT and two-photon excitation (TPE)-PDT agents.