Intravenous delivery of enzalutamide based on high drug loading multifunctional graphene oxide nanoparticles for castration-resistant prostate cancer therapy

BACKGROUND: Enzalutamide (Enz) has shown limited bioavailability via oral administration. Castration-resistant prostate cancer (CRPC) is frequent among patients receiving 18–24 months of androgen deprivation therapy. The nonsteroidal anti-androgen enzalutamide (Enz) used in the treatment of prostate cancer has shown limited bioavailability via oral administration. Therefore, we developed a multifunctional enzalutamide-loaded graphene oxide nanosystem (TP-GQDss/Enz) for CRPC intravenous treatment, with high drug loading efficiency. METHODS: Aminated graphene quantum dots (GQDs) were first cross-linked via disulfide bonds into a graphene quantum dot derivative of approximately 200 nm (GQDss), which was further functionalized with a tumour-targeting peptide and PEG to form TP-GQDss. Enz was loaded into TP-GQDss for in vitro and in vivo study. RESULTS: The results showed that high drug-loading efficiency was achieved by TP-GQDss via π–π electron interaction. TP-GQDss could be rapidly internalized by CRPC cells via endocytosis. Moreover, Enz in TP-GQDss could inhibit the growth of C4-2B and LNCaP prostate cancer cell lines in vitro. Further, TP-GQDss exhibited an enhanced cancer-targeting ability and alleviated the side effects of Enz in vivo. CONCLUSIONS: The multifunctional nanocarrier constructed here could accomplish controlled Enz release and serve as an intravenous therapy platform for CRPC. [Image: see text]