Enhanced in vivo antitumor efficacy through the nanodiamond mediated co-delivery of drugs

Combination chemotherapy can slow the emergence of resistance, but can also lead to a significant exacerbation of off-target effects. Mediated drug release can ameliorate this situation: in this study, mitoxantrone (MTO) and doxorubicin (DOX) were co-loaded onto a nanodiamond (ND) scaffold, through physical adsorption, to prepare an ND/MTO/DOX (NMD) nanodrug. The drug loading of MTO and DOX were 119 ± 3 μg mg −1 and 60 ± 3 μg mg −1 , respectively. This NMD exhibits excellent stability with negligible drug leakage upon storage. The NMD nanoparticles enter cells via the clathrin and caveolae co-mediated endocytosis pathways and primarily remain within the lysosomes. Cytotoxicity tests showed that the NMD has an enhanced synergistic effect compared with an ND loaded with either drug alone, and has a slow but effective rate of drug release. Intraperitoneal injection of the NMD-drug into tumor-bearing mice demonstrated that the NMD rapidly localizes to the tumor site with very limited dispersion to other organs. The NMD strongly suppressed tumor growth in vivo with significantly reduced toxic side effects compared to mice treated with the free drugs. These results suggest that the as-prepared NMD has potential clinical applications for the targeted co-delivery of multiple chemotherapeutics.