Enhancing chemotherapeutic efficiency through enriched drug load and controlled drug release is urgent for alleviating the suffering of cancer patients. Here, a novel pH-sensitive nanomedicine was constructed to acquire high drug loading capacity and better therapeutic efficiency. Interestingly, with the assistance of a pH 8.0 sodium borate buffer solution, PEGylated nanodiamond vehicles loaded with doxorubicin (DOX) achieved nearly 50% loading efficiency, low premature drug release in physiological conditions and effective stimuli-response release under a tumor microenvironment. In addition, assessment by flow cytometry and cell migration assay illustrated that NP/D could induce cell apoptosis, cycle abnormality and inhibit cell migration. The results from the confocal fluorescence microscopy study showed that NP/D could be internalized into cells and distributed into the cytoplasm, subsequently DOX detaches from NP/D and could migrate and enter the nucleus to inhibit cell proliferation. NP/D can open the window for new nanodrugs for a broad spectrum of anticancer agents.