Efficient Triplet-Triplet Annihilation-Based Upconversion for Nanoparticle Phototargeting.

High-efficiency upconverted light would be a desirable stimulus for triggered drug delivery. Here we present a general strategy to achieve photoreactions based on triplet-triplet annihilation upconversion (TTA-UC) and Förster resonance energy transfer (FRET). We designed PLA-PEG micellar nanoparticles containing in their cores hydrophobic photosensitizer and annihilator molecules which, when stimulated with green light, would undergo TTA-UC. The upconverted energy was then transferred by FRET to a hydrophobic photocleavable group (DEACM), also in the core. The DEACM was bonded to (and thus inactivated) the cell-binding peptide cyclo-(RGDfK), which was bound to the PLA-PEG chain. Cleavage of DEACM by FRET reactivated the PLA-PEG-bound peptide and allowed it to move from the particle core to the surface. TTA-UC followed by FRET allowed photocontrolled binding of cell adhesion with green light LED irradiation at low irradiance for short periods. These are attractive properties in phototriggered systems.