Design and Synthesis of an Aggregation-Induced Emission-Active Quad-Functional “Curcumin-Spiced Marvel” for Engineering of Sialic Acid-Targeted Nanoplatform for Cancer Therapy

Aggregation-Induced Emission (AIE) is a feature of fluorophores that overcomes the demerits of Aggregation-Caused Quenching (ACQ), which limits the utility of traditional dyes in cancer bioimaging. Tetraphenylethene (TPE) is the prototypical AIEgen among the very few compounds with this property. However, it lacks inherent targeting specificity or therapeutic functions. In an attempt to design an AIE-active, target-specific therapeutic agent, we herein report a quad-functional AIEgen derived from the golden spice - curcumin. The "Golden Spiced AIEgen" was engineered by introducing a phenylboronic acid group into curcumin, imparting pH-responsive and sialic acid-targeting properties. Further integration into self-assembling amphiphilic micelles co-loaded with chemotherapeutics enabled effective loading with extended release. The integrated nanosystem was fully biocompatible with noncancerous cells while effectively killing HepG2 liver cancer cells through sialic acid-mediated AIEgen uptake. It acted synergistically with chemotherapeutic drugs for improved treatment outcomes, and its efficacy was corroborated in hepatocarcinoma in vivo.