A hyaluronic-based prodrug with aggregation-induced emission for drug delivery and cellular imaging

AbstractA novel drug molecule (R6) is conjugated to hyaluronic acid (HA) to form a pH-responsive prodrug with aggregation-induced emission (AIE) property. Owing to its amphiphilic nature, the prodrug could self-assemble into nanoparticles (NP) in an aqueous solution. This formulation thereby gave rise to AIE of the R6 moieties which resided in the NP core. The polymer could release the drug at the tumor microenvironment (TME) acidic condition (99% release after 72 h), while remaining stable at the physiological pH. In addition, fluorescence signals by AIE from the NP could be used for cellular imaging. The hyaluronic acid shell can target the overexpressed CD44 receptors in cancer cells, which gives the NP active targeting property. The prodrug showed toxicity against the mouse breast cancer cell line 4T1 while being harmless to the L929 fibroblast cells. Fluorescence microscopy images confirmed the imaging ability of the NP in 4T1 cells. The HA-R6 polymer prodrug promises to be a versatile pH-sensitive drug delivery platform.Keywords: Hyaluronic acidprodrugdrug deliveryaggregation-induced emissionimaging AcknowledgmentsWe would like to express their gratitude to National Taiwan University of Science and Technology (NTUST) and the Department of Chemical Engineering for their support to this project. For the chemical characterization and cell studies, Taiwan Ministry of Science and Technology funding (NSTC 111-2221-E-011-025) was used. Hyluronic acid was purchased from the NSTC 109-2222-E-011-004 grant.Disclosure statementThe authors declare no competing financial interest.