Aggregation-Induced Emission (AIE) Dots: Emerging Theranostic Nanolights

Theranostic nanolights refer to luminescent nanoparticles possessing both imaging and therapeutic functions. Their shape, size, surface functions, and optical properties can be precisely manipulated through integrated efforts of chemistry, materials, and nanotechnology for customized applications. When localized photons are used to activate both imaging and therapeutic functions such as photodynamic or photothermal therapy, these theranostic nanolights increase treatment efficacy with minimized damage to surrounding healthy tissues, which represents a promising noninvasive nanomedicine as compared to conventional theranostic approaches. As one of the most promising theranostic nanolights, organic dots with aggregation-induced emission (AIE dots) are biocompatible nanoparticles with a dense core of AIE fluorogens (AIEgens) and protective shells, whose sizes are in the range of a few to tens of nanometers. Different from conventional fluorophores that suffer from aggregation-caused quenching (ACQ) due to π-π stacking interaction in the aggregate state, AIEgens emit strongly as nanoaggregates due to the restriction of intramolecular motions. Through precise molecular engineering, AIEgens could also be designed to show efficient photosensitizing or photothermal abilities in the aggregate state. Different from ACQ dyes, AIEgens allow high loading in nanoparticles without compromised performance, which makes them the ideal cores for theranostic nanolights to offer high brightness for imaging and strong photoactivities for theranostic applications. In this Account, we summarize the recent advance of AIE dots and highlight their great potential as theranostic nanolights in biomedical applications. Starting from the design of AIEgens, the fabrication of AIE dots and their bioimaging applications are discussed. The exceptional advantages of superbrightness, high resistance to photobleaching, lack of emission intermittency, and excellent biocompatibility have made them reliable cross platform contrast agents for different imaging techniques such as confocal microscopy, multiphoton fluorescence microscopy, super-resolution nanoscopy, and light-sheet ultramicroscopy, which have been successfully applied for cell tracking, vascular disease diagnosis, and image-guided surgery. The integration of therapeutic functions with customized AIEgens has further empowered AIE dots as an excellent theranostic platform for image-guided phototherapy. Of particular interest is AIE photosensitizer dots, which simultaneously show bright fluorescence and high photosensitization, yielding superior performance to commercial photosensitizer nanoparticles in image-guided therapy. Further development in multiphoton excited photodynamic therapy has offered precise treatment with up to 5 μm resolution at 200 μm depth, while chemiexcited photodynamic therapy has completely eliminated the limitation of penetration depth to realize power-free imaging and therapy. With this Account, we hope to stimulate more collaborative research interests from different fields of chemistry, materials, biology, and medicine to promote translational research of AIE dots as the theranostic nanolights.