Differentially engineered nano-tracker of intracellular drug for potentiating breast cancer treatment

Small-molecule self-assembled nanomedicines have shown considerable promise in anticancer therapy. However, the majority of these drugs are composed of the active drug, tumor-responsive chemical linkers, and assembly modules, which significantly complicate the synthesis process. Furthermore, the mechanisms underlying the cellular uptake and drug release of these tumor-responsive self-assembled nanodrugs remain unclear. To overcome these challenges, we exploit a differentially engineered nano-tracker, allowing real-time monitoring of changes in fluorescence intensity. The nano-tracker is elaborately self-assembled by a functional conjugate (artesunate-tetraphenylethylene, Art-TPE), which eliminates the sensitive linkers. Notably, such a functional conjugate not only retains effective anti-tumor activity, but renders a 2-fold aggregation-induced emission (AIE) effect enhancement compared to TPE. As expected, such a differentially engineered nano-tracker displays effective anti-tumor activity in vitro and in vivo. This study offers valuable insights into the development of small-molecule-based nanomedicines for more efficient diagnostic and therapeutic strategies.