Exploration of all-natural aggregation-induced emission nanoparticles from co-assembly of bioactive herbal molecules

Nanoparticles with aggregation-induced emission (AIE) have been identified as promising functional nanomaterials for bioimaging applications, characterized by their high luminescent efficiency, tunable emission properties, and ease of preparation. Nonetheless, the majority of AIE-active nanoparticles reported to date encounter many of the challenges such as intricate organic synthesis, elevated costs, limited water solubility, and low biocompatibility, which significantly constrain their practical bio-related applications. To address these limitations, the co-assembly of natural small molecules extracted from Chinese herbal medicines to construct AIE-active nanoparticles is of great significance, as they are readily accessible and water dispersible, and have excellent biocompatibility. In this work, glycyrrhizic acid (GA), berberine (BR), and tannic acid (TA) are found to spontaneously co-assemble into stable and homogeneous nanoparticles (GA n BR n TA n -NPs) in aqueous solution through non-covalent interactions including electrostatic interactions, hydrogen bonding, and π-π stacking. The multicomponent co-assembly and interactions effectively restrict the intramolecular motion of BR and thereby endow the GA n BR n TA n -NPs with remarkable and stable AIE properties. These AIE nanoparticles can be used as a carrier-free delivery system, which displays a sustained release behavior of BR, while maintain their fluorescence during simulated gastrointestinal delivery and digestion. Cytotoxicity and cellular imaging tests confirm that the GA n BR n TA n -NPs have good biocompatibility and can emit bright green fluorescence after uptake by Caco-2 cells. This study provides an eco-friendly, mild, and simple process of fabricating all-natural AIE-active nanoparticles with improved aqueous dispersibility, satisfactory fluorescence properties, and high biocompatibility, which are promising for carrier-free cargo delivery and cell imaging applications.