title: Highly efficient, conjugated-polymer-based nano-photosensitizers for selectively targeted two-photon photodynamic therapy and imaging of cancer cells.
abstract: 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.
authors.affiliation: Department of Chemistry, National University of Singapore, 3 Science Drive 3, 117543 Singapore (Singapore).
authors.forename: Xiaoqin
authors.initials: X
authors.lastname: Shen
authors.forename: Shuang
authors.initials: S
authors.lastname: Li
authors.forename: Lin
authors.initials: L
authors.lastname: Li
authors.forename: Shao Q
authors.initials: SQ
authors.lastname: Yao
authors.forename: Qing-Hua
authors.initials: QH
authors.lastname: Xu
mesh_terms: D006801:Humans; D053758:Nanoparticles / Q000737:chemistry*; D009369:Neoplasms / Q000737:chemistry*; D010778:Photochemotherapy / Q000379:methods*; D017785:Photons; D017319:Photosensitizing Agents / Q000494:pharmacology*; D011108:Polymers / Q000737:chemistry*
chemical_list: D017319:Photosensitizing Agents; D011108:Polymers
keywords: energy transfer; imaging agents; nanoparticles; photodynamic therapy; polymers