A viscosity-activable nano-micelle with aggregation-induced emission for boosting NIR-II fluorescence imaging-guided synergetic photodynamic/photothermal therapy of breast cancer

In view of the fast-growing achievements of cancer phototheranostics, the exploration of advanced materials shows inexhaustible and vigorous vitality. To overcome those limitations of existing materials, such as aggregation-caused fluorescence quenching, inferior selectivity, and high O₂-dependence, the utilization of specific activatable agents with aggregation-induced emission (AIE) features is highly desirable yet remains challenging. Herein, we have designed an organic small-molecule microenvironment activated AIE agent, namely DPXBI. After encapsulation into amphiphilic DSPE-PEG-RGD through self-assembly, the biocompatibility, water solubility, targeting effect, and circulation time in the blood of obtained nano-micelle ^RM@DPXBI are improved. ^RM@DPXBI showed powerful fluorescence in the second near-infrared (NIR-II) region after being activated by viscosity in the tumor microenvironment, which could accurately identify the boundary of the tumor and determine the optimal accumulation time for following phototherapy. Subsequently, ^RM@DPXBI exerts inhibiting on breast cancer growth through synergistic photodynamic (PDT) and photothermal (PTT) therapy under single laser irradiation. Meanwhile, the phototherapy-induced cellular death increases intracellular viscosity, which further restricts the intramolecular motion of ^RM@DPXBI, resulting in the amplifying of PDT effect. The activated strategy provides a new exploration for the design and development of AIE and viscosity activation agents in tumor theranostics.