Top-down bioinspired nanotheranostics with AIE luminogens

The advances in nanotechnology have been coupled with a growing interest in and extensive research on nanodrug delivery systems (NDDS). NDDS represent a revolutionary approach to therapeutic delivery at the molecular level. Notwithstanding the research efforts and potential preclinical results, few NDDS have successfully transitioned to clinical applications. A major obstacle in this translation process with the “bottom-up” NDDS strategy is the severe protein crown effect. Herein, proteins in the biological environment form a corona around the outer shell of NDDS, thereby preventing rationally designed NDDS from achieving their expected targeting capabilities and causing off-target effects that compromise the therapeutic efficacy. To circumvent this, the innovative concept of bionic nano-based drug delivery systems (BNDDS) is investigated extensively as a “top-down” concept that leverages bacteria, exosomes, viruses, cell membranes, and cellular organelles as delivery cargo. BNDDS demonstrate superior cell targetability, stability, and immune response during drug delivery. These have potential clinical applications when combined with aggregation-induced emission (AIE) fluorophores, which have exceptional controllability, negligible toxicity, and remarkable photostability. Therefore, we present a comprehensive overview of various engineering approaches for “top-down”-based AIE-functionalized BNDDS, enable to provide long-term imaging capabilities and sustained therapeutic effects crucial for accurate diagnosis and effective treatment protocols.