Water‐Soluble Conjugated Polymers for Simultaneous Two‐Photon Cell Imaging and Two‐Photon Photodynamic Therapy

Conventional photosensitizers generally suffer from low efficiency in novel non‐invasive two‐photon photodynamic cancer therapy due to their small two‐photon absorption cross section and they lack an imaging capability for therapy guiding due to their low fluorescence yield. Demonstrated here is the first water‐soluble conjugated polymers as direct two‐photon photosensitizers with dual capability of two‐photon cell imaging and two‐photon photodynamic therapy. By introducing a strong electron‐withdrawing cyano group into the phenyl ring of the backbone, the cyano‐substituted poly(fluorene‐2,7‐ylenevinylene‐co‐phenylene) (PFVCN) displays a 2.4 times higher maximum two‐photon absorption cross section per repeat unit and significantly higher fluorescence quantum yield in water than the unsubstituted PFV. The large two‐photon absorption cross section of PFVCN allows it to efficiently generate singlet oxygen under two‐photon excitation, which is critical for two‐photon photodynamic therapy. Two‐photon excitation cell imaging and efficient two‐photon‐induced photodynamic therapy effect on cancer cells of PFVCN are successfully demonstrated. These studies provide insight in designing novel photosensitizing agents for simultaneous two‐photon imaging and two‐photon photodynamic therapy, which allows two‐photon imaging guided therapy to fully take the unique advantages of two‐photon excitation such as deep penetration and 3D selectivity. A series of water‐soluble conjugated polymers with large two‐photon absorption cross section are synthesized. PFVCN is found to display high fluorescence brightness and a high singlet oxygen generation capability under two‐photon excitation. Its potential application as a promising agent for simultaneous two‐photon imaging and two‐photon photodynamic therapy are demonstrated.