Nanodiamond-conjugated transferrin as chemotherapeutic drug delivery

•The ND-(Tf-DOX) system can target drug delivery in vitro and inhibit tumor growth with low side effects in vivo.

Targeted therapy is considered to be a promising strategy of cancer treatments. Herein we demonstrate the potential of a nanotechnology strategy for special drug delivery based on nanodiamond (ND) functionalized by transferrin. Specifically, the transferrin–doxorubicin (Tf–DOX) complex is covalently coupled with carboxylated ND to prepare the targeted nanomedicine (ND-(Tf–DOX)). In vitro studies showed that ND-(Tf–DOX) can effectively deliver the drug inside living cells via a clathrin-dependent and transferrin receptor-mediate endocytosis pathway by flow cytometry analysis, and the ND-(Tf–DOX) nanomedicine located in the lysosomes through laser scanning confocal microscopy. In vivo, we found that tumor volume change of tumor-bearing mice treated with ND-(Tf–DOX) nanomedicine was lightly lower than that of DOX-treated. The results demonstrated that the targeting capability of ND-(Tf–DOX) nanomedicine relative drug alone is not significant, and it may be disturbed by proteins when they are placed in a complex biological environment. However, it can markedly decrease side effects compared to DOX alone in both the liver and spleen. This suggests that in vivo ND-(Tf–DOX) nanomedicine can effectively inhibit tumor growth as the same as DOX. More importantly, it can decrease side effects. This study attempts to endowed transferrin-functionalized and chemotherapeutic drug-loaded nanodiamond as a platform for drug delivery and therapy to cancer cells.

Graphical abstractThe drug system ND-(Tf–DOX) tends to selectively target tumor cells with overexpressed TfR and enter the cells by clathrin-dependent and transferrin receptor-mediated endocytosis. In addition, ND-(Tf–DOX) nanoparticles not only played a slow and sustained drug release profile, and but also had a tumor-targeted toxicity in vitro. In vivo ND-(Tf–DOX) nanomedicine can effectively inhibit tumor growth as the same as DOX. Much importantly, it can decrease side effects. This implies that ND-(Tf–DOX) can act as a nanodrug with promising chemotherapeutic efficacy and safety.Figure optionsDownload full-size imageDownload as PowerPoint slide