Abstract
Intracellular singlet oxygen ((1)O(2)) generation and detection help optimize the outcome of photodynamic therapy (PDT). Theranostics programmed for on-demand phototriggered (1)O(2) release and bioimaging have great potential to transform PDT. We demonstrate an ultrasensitive fluorescence turn-on sensor-sensitizer-RGD peptide-silica nanoarchitecture and its (1)O(2) generation-releasing-storing-sensing properties at the single-particle level or in living cells. The sensor and sensitizer in the nanoarchitecture are an aminomethyl anthracene (AMA)-coumarin dyad and a porphyrin or CdSe/ZnS quantum dots (QDs), respectively. The AMA in the dyad quantitatively quenches the fluorescence of coumarin by intramolecular electron transfer, the porphyrin or QD moiety generates (1)O(2,) and the RGD peptide facilitates intracellular delivery. The small size, below 200 nm, as verified by scanning electron microscopy and differential light scattering measurements, of the architecture within the (1)O(2) diffusion length enables fast and efficient intracellular fluorescence switching by the tandem ultraviolet (UV)-visible or visible-near-infrared (NIR) photo-triggering. While the red emission and (1)O(2) generation by the porphyrin are continually turned on, the blue emission of coumarin is uncaged into 230-fold intensity enhancement by on-demand photo-triggering. The (1)O(2) production and release by the nanoarchitecture enable spectro-temporally controlled cell imaging and apoptotic cell death; the latter is verified from cytotoxic data under dark and phototriggering conditions. Furthermore, the bioimaging potential of the TCPP-based nanoarchitecture is examined in vivo in B6 mice.