Engineered Targeted Hyaluronic Acid-Glutathione-Stabilized Gold Nanoclusters/Graphene Oxide-5-Fluorouracil as a Smart Theranostic Platform for Stimulus-Controlled Fluorescence Imaging-Assisted Synergetic Chemo/Phototherapy

A theranostic platform with integrated diagnostic and therapeutic functions as well as specific targeted and controlled combination therapy to enhance treatment efficacy is of great importance for a wide range of biomedical applications. Here, we first attempted to develop biocompatible hyaluronic acid (HA)-glutathione (GSH) conjugate stabilized gold nanoclusters (GNCs) combined with graphene oxide (GO), accompanied by loading 5-fluorouracil (5FU), as a novel theranostic platform (HG-GNCs/GO-5FU, HG refers to HA-GSH). Multifunctional HG-GNCs possessed excellent fluorescence, photosensitivity and specific targeting ability to the cancer cells while their fluorescence and singlet oxygen generation could be strongly inhibited by GO and then effectively restored by lysosomal hyaluronidase in tumor cells. The sustained and complete release of 5FU from HG-GNCs/GO could also be stimulated successively by enzymatic degradation of HA and light-induced heat effect of GO under laser irradiation so that turn-on cell imaging-assisted synergistic therapeutic strategies associated with triple enzyme/light-controlled chemo/photothermal/photodynamic therapy could be achieved at the same time, reducing greatly the side effects of materials to normal cells. Our study presents a novel strategy to combine targeting and bioimaging with triple therapies to enhance the antitumor effect.