Highly efficient, conjugated-polymer-based nano-photosensitizers for selectively targeted two-photon photodynamic therapy and imaging of cancer cells.

Two-photon photodynamic therapy (2P-PDT) is a promising noninvasive treatment of cancers and other diseases with three-dimensional selectivity and deep penetration. However, clinical applications of 2P-PDT are limited by small two-photon absorption (TPA) cross sections of traditional photosensitizers. The development of folate receptor targeted nano-photosensitizers based on conjugated polymers is described. In these nano-photosensitizers, poly{9,9-bis[6''-(bromohexyl)fluorene-2,7-ylenevinylene]-co-alt-1,4-(2,5-dicyanophenylene)}, which is a conjugated polymer with a large TPA cross section, acts as a two-photon light-harvesting material to significantly enhance the two-photon properties of the doped photosensitizer tetraphenylporphyrin (TPP) through energy transfer. These nanoparticles displayed up to 1020-fold enhancement in two-photon excitation emission and about 870-fold enhancement in the two-photon-induced singlet oxygen generation capability of TPP. Surface-functionalized folic acid groups make these nanoparticles highly selective in targeting and killing KB cancer cells over NIH/3T3 normal cells. The 2P-PDT activity of these nanoparticles was significantly improved, potentially up to about 1000 times, as implied by the enhancement factors of two-photon excitation emission and singlet oxygen generation. These nanoparticles could act as novel two-photon nano-photosensitizers with combined advantages of low dark cytotoxicity, targeted 2P-PDT with high selectivity, and simultaneous two-photon fluorescence imaging capability; these are all required for ideal two-photon photosensitizers.