Smart pH-responsive and high doxorubicin loading nanodiamond for in vivo selective targeting, imaging, and enhancement of anticancer therapy

Abstract

Nanodiamond as a carrier for transporting chemotherapy drugs has emerged as a promising strategy for treating cancer. However, several factors have limited its extensive applications in biology, such as low drug loading, tending to aggregate and high drug loss under physiological conditions. In this work, to ensure a high drug capacity and low drug leakage in blood circulation, and especially to ensure that it is delivered to the tumor region, a smart pH-responsive drug delivery system is designed and prepared using doxorubicin (DOX) adsorbed onto PEGylated nanodiamond in sodium citrate medium (ND–PEG–DOX/Na₃Cit, NPDC). The system can significantly enhance cellular uptake to exert a therapeutic effect in comparison to the free drug. And more importantly, DOX was released in a sustained and pH-dependent manner, exhibiting excellent stability under physiological conditions. In addition, NPDC could enter into cells via both the clathrin- and caveolae-mediated endocytosis pathways, and then the dissociated DOX migrated into the nucleus to block the growth of cancer cells. Furthermore, NPDC can significantly inhibit cell migration and change the cell cycle. Excitingly, the NPDC system was very smart for the effective enrichment at the tumor site in vivo and enhancing antitumor efficiency with low toxicity beyond conventional DOX treatment in cancer cells and a nude mouse model. So this study introduces a simple and effective strategy to design a promising drug delivery platform for improving the biomedical applications of the smart nanodiamond carriers.