Targeting co-delivery of doxorubicin and gefitinib by biotinylated Au NCs for overcoming multidrug resistance in imaging-guided anticancer therapy

Drug resistance and potential cardiotoxicity severely limit the DOX-mediated chemotherapy in clinical. Multidrug combination is conducive to the realization of multi-modal synergy at the molecular level, which is crucial in drug dose optimization and improvement of therapeutic effect. In this work, fluorescent biotinylated Au Nanoclusters as an active targeting carrier was developed to realize real-time biological imaging and dualdrug delivery simultaneously. DNA toxin doxorubicin (DOX) and tyrosinase inhibitor gefitinib (GEF) were selected as dual-drug models for the treatment of human non-small cell lung cancer. The in vitro and in vivo results showed that dual-drug combination suppressed cancer cell growth more efficiently than any single formula at the same concentrations. GEF can block signaling in target cancer cells with mutated and overactive EGFR, thereby inhibiting tumor growth and metastasis and promoting tumor cell apoptosis. Combined with DOX chemotherapy, it will effectively overcome the problem of DOX resistance. In addition, the dual-drug delivery system produced excellent synergistic therapeutic effects without extra adverse toxicities. It provides a reference for the design and clinical application of the dual-drug delivery system.