Molecular Engineering of High-Performance Aggregation-Induced Emission Photosensitizers to Boost Cancer Theranostics Mediated by Acid-Triggered Nucleus-Targeted Nanovectors

Phototheranostics involving both fluorescence imaging and photodynamic therapy has been recognized to be potentially powerful for cancer treatment by virtue of various intrinsic advantages. However, the state-of-the-art materials in this area are still far from ideal toward practical applications, ascribed to their respective and collective drawbacks, such as inefficient imaging quality, inferior reactive oxygen species (ROS) production, the lack of subcellular-targeting capability, and dissatisfactory delivery. In this paper, these shortcomings are successfully addressed through the integration of finely engineered photosensitizers with aggregation-induced emission (AIE) features and well tailored nanocarrier systems. The yielded AIE NPs simultaneously exhibit broad absorption in the visible-light region, bright near-infrared fluorescence emission, high ROS generation, as well as tumor lysosomal acidity-activated and nucleus-targeted delivery functions, making them promising for precise and efficient phototheranostics. Both <i>in vitro</i> and <i>in vivo</i> evaluations show that the presented nanotheranostic systems bearing good photostability and appreciable biosecurity perform well in fluorescence imaging-guided photodynamic cancer therapy. This study thus not only extends the application scopes of AIE nanomaterials but also offers useful insights into constructing advanced cancer phototheranostics.