Redox-responsive dasatinib-containing hyaluronic acid prodrug and co-delivery of doxorubicin for cancer therapy

Redox-responsive prodrugs were synthesized by conjugating dasatinib (Das)/cholesterol (Chol) to hyaluronic acid (HA) via the cystamine dihydrochloride (Cys), and hexamethylene diamine (Hda) linkers. In a redox environment (10 mM dithiothreitol, DTT), a substantial amount of the grafted Das was released and faster than that observed under physiological conditions. The cytotoxicity of redox-sensitive HA-Cys-P(SSDas/CCChol) was greater than that of redox-insensitive HA-Hda-PCCDas. Flow cytometry showed that the uptake of HA-targeted DOX–encapsulated micelles was faster than that of free DOX.