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Owing to their unique optical properties (e.g., bright fluorescence coupled with strong photostability) and negligible toxicity, fluorescent silicon nanoparticles (SiNPs) have been demonstrated to be promising probes for bioimaging analysis. Herein, we describe the use of Caenorhabditis elegans (C. elegans) as an animal model to investigate the in vivo behavior and molecular imaging capacity of ultrasmall fluorescent SiNPs (e.g., ~ 3.9 ± 0.4 nm). Our studies show that (1) the internalized SiNPs do not affect the morphology and physiology of the worms, suggesting the superior biocompatibility of SiNPs in live organisms; (2) the internalized SiNPs cannot cross the basement membrane of C. elegans tissues and they display limited diffusion ability in vivo, providing the possibility of their use as nanoprobes for specific tissue imaging studies in intact animals; (3) more than 80% of the fluorescence signal of internalized SiNPs remains even after 120 min of continuous laser bleaching, whereas only ~20% of the signal intensity of mCherry or cadmium telluride quantum dots remains under the same condition, indicating the robust photostability of SiNPs in live organisms; and (4) cyclic RGD-peptide-conjugated SiNPs can specifically label muscle attachment structures in live C. elegans, which is the first proof-of-concept example of SiNPs for targeted molecular imaging in these live worms. These finding raise exciting opportunities for the design of high-quality SiNP-based fluorescent probes for long-term and real-time tracking of biological events in vivo.
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