Aptamer-Functionalized Gold Nanostars for on-Demand Delivery of Anticancer Therapeutics

Gold nanostars (AuNS) are promising carriers for targeted delivery of therapeutic oligonucleotides, but their potential in fabricating an on-demand drug release system in a facile and robust way remains to be explored. In this paper, we used a model aptamer (HApt), acting not only as a target ligand but also as a natural thermal-responsive material, to decorate AuNS. The prepared gold nanoconstruct, HApt@AuNS, displayed stoichiometric loading capacity of the anthracycline drug doxorubicin (Dox). The on-demand drug release was realized by illuminating nanoconstructs with near-infrared (NIR) light. Furthermore, a higher degree of Dox release from the nanoconstructs was achieved in an acidic environment, compared to neutral conditions. The in vitro experiments showed that Dox-intercalation did not affect the cell uptake efficiency of HApt@AuNS, which could enter cells through clathrin-mediated endocytosis and microtubule-dependent active transport to lysosomes. Dox-loaded HApt@AuNS exhibited intracellular on-demand drug release and enhanced toxicity against cancer cells by NIR-irradiation.