Antibody-Conjugated Nanodiamond Enzyme for Targeted Non-Small-Cell Lung Cancer by Regulating Oxidative Stress

Understanding the biocompatibility and efficiency of nanodiamond enzymes (NDE) is crucial for evaluating their potential risks and applications to human health. In previous research, ultrapure NDE was synthesized by using laser ablation in liquid (LAL), and the enzyme-like activities for immunoassay and antioxidant applications were analyzed in detail. However, the possible bioapplications in the tumor were not considered. Here, the optimal fluorescent intensities of NDE were observed in human lung cancer cells and zebrafish. Moreover, the NDE-conjugated specific antibodies NDE/P40 and NDE/TTF-1 (thyroid transcription factor-1) could accurately target lung cancer cells in vitro and in vivo. Consequently, NDE/P40 and NDE/TTF-1 were highly effective in inhibiting lung tumorigenesis and significantly improved the survival of mice with xenografts. The mechanisms were as follows: (1) induced oxidative stress, resulting in the collapse of the mitochondrial membrane potential and mitochondria-dependent cell death; (2) catalyzed the production of oxygen by H2O2, reversing the hypoxic environment within the tumor; and (3) inhibited NF-κB activation, leading to a significant inhibition of the AKT-STAT3 survival cascade. Our data establish that "nanospur-like" antibodies conjugated NDE can potentially be an effective and biocompatible treatment for non-small-cell lung cancer by targeting the regulation of oxidative stress.