Abstract
It is urgent to improve the stability of drug system and enhance the curative effect of efficient cancer chemotherapy. In this study, an aminocaproic acid modified nanodiamond-based prodrug (ND-ACA-HYD-DOX NAHD) with pH-activatable fluorescence and cytotoxicity was designed and synthesized. More importantly, the as-synthesized prodrug possessed excellent stability under pH 7.4, along with quenched fluorescence of doxorubicin (OFF). In addition, the drug release profile showed that NAHD nanoparticles released large amounts of DOX under acidic environment with endosomes, implying that the acylhydrazone linkage of NAHD was broken. Excitingly, results of cellular activity and apoptosis assays revealed that NAHD displayed comparable therapeutic efficiency to that of free DOX. Thus, our design proved that the as-synthesized prodrug exhibited obvious response in tumor microenvironment (TME), which greatly reduced the toxic and side effects.
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