Singlet oxygen sensitization by organic molecules is a topic of major interest in the developmentof both efficient photodynamic therapy (PDT) and aerobic oxidations under complete green chemistryconditions. We report on the design, synthesis, biology, and complete spectroscopic characterization (vis-NIR linear and two-photon absorption spectroscopy, singlet oxygen generation efficiencies for both one-and two-photon excitation, electrochemistry, intrinsic dark toxicity, cellular uptake, and subcellular localization)of three classes of innovative singlet oxygen sensitizers pertaining to the family of symmetric squarainederivatives originating from
-excessive heterocycles. The main advantage of
-extended squarainephotosensitizers over the large number of other known photosensitizers is their exceedingly strong two-photon absorption enabling, together with sizable singlet oxygen sensitization capabilities, for their use atthe clinical application relevant wavelength of 806 nm. We finally show encouraging results about the darktoxicity and cellular uptake capabilities of water-soluble squaraine photosensitizers, opening the way forclinical small animal PDT trials.