Fluorescent silicon nanoparticles (SiNPs), resembling a typical zero-dimensional silicon nanomaterial, have shown great potential in a wide range of biological and biomedical applications. However, information regarding the toxicity of this material in live organisms is still very scarce. In this study, we utilized Caenorhabditis elegans (C. elegans), a simple but biologically and anatomically well-described model, as a platform to systematically investigate the in vivo toxicity of SiNPs in live organisms at the whole-animal, cellular, subcellular, and molecular levels. We calculated the effect of SiNPs on C. elegans body length (N ≥ 75), lifespan (N ≥ 30), reproductive capacity (N ≥ 10), endocytic sorting (N ≥ 20), endoplasmic reticulum (ER) stress (N ≥ 20), mitochondrial stress (N ≥ 20), oxidative stress (N ≥ 20), immune response (N ≥ 20), apoptosis (N ≥ 200), hypoxia response (N ≥ 200), metal detoxification (N ≥ 200), and aging (N ≥ 200). The studies showed that SiNPs had no significant effect on development, lifespan, or reproductive ability (p > 0.05), even when the worms were treated with a high concentration (e.g., 50 mg/mL) of SiNPs at all growth and development stages. Subcellular analysis of the SiNP-treated worms revealed that the intracellular processes of the C. elegans intestine were not disturbed by the presence of SiNPs (p > 0.05). Toxicity analyses at the molecular level also demonstrated that the SiNPs did not induce harmful or defensive cellular events, such as ER stress, mitochondria stress, or oxidative stress (p > 0.05). Together, these findings confirmed that the SiNPs are low in toxicity and biocompatible, supporting the suggestion that the material is an ideal fluorescent nanoprobe for wide-ranging biological and biomedical applications.
