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Ag2Se quantum dots (QDs) are novel fluorescent probes in the second near-infrared window with great imaging quality and biocompatibility. Surface modification is an essential step to disperse Ag2Se QDs into biological fluids, and endow Ag2Se QDs with diverse surface chemistry. However, the effect of surface chemistry on the biological behaviors and chemical fates of Ag2Se QDs has not been studied, which hinders the design of suitable Ag2Se QDs for biomedical applications. Here, the distribution, degradation, excretion and toxicity of 2-aminoethanethiol and mercaptopropionic acid coated Ag2Se QDs (denoted as QDs-MEA and QDs-MPA, respectively) were systematically investigated in mice for a 28-day observation period after a single intravenous injection. Ag2Se QDs with different surface chemistries displayed similar trends in all observations, such as fast blood clearance, main uptake in the liver and spleen, severe biotransformation, Ag excretion through feces, and low toxicity. The major different behaviors observed were the partially pulmonary deposition, the faster transformation at the initial stage, the lower excretion percentage, and the more obvious damage to the liver by QDs-MEA compared to QDs-MPA. The surface chemistry of Ag2Se QDs regulated their biological behaviors and chemical fates in vivo, and surface chemistry should be fully regarded when designing Ag2Se QDs for biomedical applications from the biosafety perspective.

Lanthanide-doped upconversion nanoparticles can convert long wavelength excitation radiation to short wavelength emission. They have great potential in biomedical applications, such as bioimaging, biodetection, drug delivery, and theranostics. However, there is little information available on their bioavailability and biological effects after oral administration. In this study, we systematically investigated the bioavailability, biodistribution, and toxicity of silica-coated upconversion nanoparticles administrated by gavage. Our results demonstrate that these nanoparticles can permeate intestinal barrier and enter blood circulation by microstructure observation of Peyer's patch in the intestine. Comparing the bioavailability and the biodistribution of silica-coated upconversion nanoparticles with oral and intravenous administration routes, we found that the bioavailability and biodistribution are particularly dependent on the administration routes. After consecutive gavage for 14 days, the body weight, pathology, Zn and Cu level, serum biochemical analysis, oxidative stress, and inflammatory cytokines were studied to further evaluate the potential toxicity of the silica-coated upconversion nanoparticles. The results suggest that these nanoparticles do not show overt toxicity in mice even at a high dose of 100 mg/kg body weight.

The surface chemistry of Ag2Se QDs regulated their distribution, metabolism, excretion and toxicity in mice.

As a novel fluorescent probe in the second near-infrared window, Ag2Se quantum dots (QDs) exhibit great prospect in in vivo imaging due to their maximal penetration depth and negligible background. However, the in vivo behavior and toxicity of Ag2Se QDs still largely remain unknown, which severely hinders their wide-ranging biomedical applications. Herein, we systematically studied the blood clearance, distribution, transformation, excretion, and toxicity of polyethylene glycol (PEG) coated Ag2Se QDs in mice after intravenous administration with a high dose of 8 μmol/kg body weight. QDs are quickly cleared from the blood with a circulation half-life of 0.4 h. QDs mainly accumulate in liver and spleen and are remarkably transformed into Ag and Se within 1 week. Ag is excreted from the body readily through both feces and urine, whereas Se is excreted hardly. The toxicological evaluations demonstrate that there is no overt acute toxicity of Ag2Se QDs to mice. Moreover, in regard to the in vivo stability problem of Ag2Se QDs, the biotransformation and its related metabolism are intensively discussed, and some promising coating means for Ag2Se QDs to avert transformation are proposed as well. Our work lays a solid foundation for safe applications of Ag2Se QDs in bioimaging in the future.