Stimuli-responsive nanotheranostic systems conjugated with AIEgens for advanced cancer bio-imaging and treatment

Aggregation-induced emission (AIE) is a unique phenomenon observed in various materials such as organic luminophores, carbon dots (CDs), organic-inorganic nanocomposites, fluorescent dye molecules, and nanoparticles (NPs). These AIE-active materials, or AIEgens, are ideal for balancing multifunctional phototheranostics and energy dissipation. AIE properties can manifest in organic fluorescent probes, rendering them effective for cancer treatment due to their ability to penetrate deeply and provide high therapeutic efficacy. This efficacy is attributed to their high photobleaching thresholds, ability to induce Stokes shifts, and capacity to activate fluorophores. Therefore, the development of innovative AIE-based materials for disease diagnosis and treatment, particularly for cancer, is both important and promising. Recent years have seen successful demonstrations of nanoparticles with AIE properties being used for photodynamic therapy (PDT) and multimodal imaging of tumor cells. These fluorophores have been shown to impact mitochondria and lysosomes, generate reactive oxygen species (ROS), activate the immune system, load and release drugs, and ultimately induce apoptosis in tumor cells. In this review, we examine previous studies on the manufacturing methods and effects of AIEgens on cancer cells, with a theranostic strategy of simultaneous treatment and imaging. We also investigate the factors affecting drug delivery on different cancer cells, including internal stimuli such as pH, ROS, enzymes, and external stimuli like near-infrared (NIR) light and ultrasound waves.