Dual-targeting SERS-encoded graphene oxide nanocarrier for intracellular co-delivery of doxorubicin and 9-aminoacridine with enhanced combination therapy

Abstract

A graphene oxide (GO)-based nanocarrier that imparts tumor-selective delivery of dual-drug with enhanced therapeutic index, is introduced. GO is conjugated with Au@Ag and Fe₃O₄ nanoparticles, which facilitates it with SERS tracking and magnetic targeting abilities, followed by the covalent binding of the anti-HER2 antibody, thus allowing it to both actively and passively target SKBR3 cells, human breast cancer cells expressed with HER2. Intracellular drug delivery behaviors are probed using SERS spectroscopy in a spatiotemporal manner, which demonstrates that nanocarriers are internalized into the lysosomes and release the drug in response to the acidic microenvironment. The nanocarriers loaded with dual-drug possess increased cancer cytotoxicity in comparison to those loaded with a single drug. Attractively, the enhanced cytotoxicity against cancer cells is achieved with relatively low concentrations of the drug, which is demonstrated to be involved in the drug adsorption status. These results may give us the new prospects to design GO-based delivery systems with rational drug dosages, thus achieving optimal therapeutic response of the multi-drug with increased tumor selectivity and reduced side effects.