Carrier-free, pure nanodrugs based on dasatinib and 5-Fluorouracil show aggregation-induced emission and enhanced antitumor efficacy

Therapies based on small molecule targeted inhibitors usually suffer from several limitations such as poor water solubility, low oral bioavailability, rapid metabolism in vivo, and dose-limiting toxicity. The aim of this paper is to prepare a carrier-free nanodrug self-delivery system by self-assembly of dasatinib (DAS) and 5-Fluorouracil (Fu). By adjusting the ratio of DAS to Fu (10:1, 5:1, 2:1, 1:1), a series of nanoparticles (DAS/F NPs) with different particle sizes can be obtained without additional chemical modifications or carrier materials. More importantly, during self-assembly, DAS/F NPs produce aggregation-induced emission (AIE) effect. This makes DAS/F NPs suitable for bioimaging and tracking cell trafficking without any fluorescent probe labeling. DAS/F NPs (2:1) with a diameter around 150 nm was selected for the next antitumor study. The cellular uptake and cytotoxicity of DAS/F NPs were measured by EMT6 and MCF-7 cells as well as the corresponding multicellular spheroids. Finally, in vivo antitumor against EMT6 tumor-bearing mice, immunohistochemical studies and hemolysis assays demonstrated DAS/F NPs possess significant synergistic antitumor effects and excellent biocompatibility.