Antibody-Conjugated\nNanodiamond Enzyme for Targeted\nNon-Small-Cell Lung Cancer by Regulating Oxidative Stress

Understanding the biocompatibility and efficiency of\nnanodiamond\nenzymes (NDE) is crucial for evaluating their potential risks and\napplications to human health. In previous research, ultrapure NDE\nwas synthesized by using laser ablation in liquid (LAL), and the enzyme-like\nactivities for immunoassay and antioxidant applications were analyzed\nin detail. However, the possible bioapplications in the tumor were\nnot considered. Here, the optimal fluorescent intensities of NDE were\nobserved in human lung cancer cells and zebrafish. Moreover, the NDE-conjugated\nspecific antibodies NDE/P40 and NDE/TTF-1 (thyroid transcription factor-1)\ncould accurately target lung cancer cells in vitro and in vivo. Consequently,\nNDE/P40 and NDE/TTF-1 were highly effective in inhibiting lung tumorigenesis\nand significantly improved the survival of mice with xenografts. The\nmechanisms were as follows: (1) induced oxidative stress, resulting\nin the collapse of the mitochondrial membrane potential and mitochondria-dependent\ncell death; (2) catalyzed the production of oxygen by H<sub>2</sub>O<sub>2</sub>, reversing the hypoxic environment within the tumor;\nand (3) inhibited NF-κB activation, leading to a significant\ninhibition of the AKT-STAT3 survival cascade. Our data establish that\n“nanospur-like” antibodies conjugated NDE can potentially\nbe an effective and biocompatible treatment for non-small-cell lung\ncancer by targeting the regulation of oxidative stress.