Vacancy-induced toxicity of CoSe₂ nanomaterials in rat lung macrophages

Rich vacancies of semiconductor nanomaterials (NMs) give rise to great enhancement of their physical and chemical properties such as magnetic, catalytic, optical, etc. These NMs possessing extensive applications could inevitably enter into the environment and increase the toxic effects on organisms, so it is imperative to investigate the cytotoxicity of NMs with different types of vacancies. Here, one-dimensional cobalt selenide (CoSe₂) NMs with different vacancies were synthesized through the same precursor while calcined at different temperatures (P-CoSe₂ which calcined at 200 °C and N-CoSe₂ which calcined at 230 °C). According to the positron annihilation spectrum, the V_SeSe vacancy associate in P-CoSe₂ was endowed with two positive charges, while the V_CoCoCoSeSe vacancy associate in N-CoSe₂ possessed four negative charges. Cell viability assays revealed that N-CoSe₂ had higher toxicity to macrophages than P-CoSe₂, which was attributed to higher levels of intracellular reactive oxygen species induced by N-CoSe₂. Further investigation showed that N-CoSe₂ had higher affinity to the mitochondrion-targeting peptide, leading to its preferential distribution in the mitochondria and consequent induction of mitochondrial superoxide production. In contrast, P-CoSe₂ exhibited higher affinity to the endoplasmic reticulum (ER)-targeting peptide, facilitating its preferential distribution in the ER and the nuclei and causing higher damage to both organelles as compared to N-CoSe₂. These results demonstrated that type of surface vacancies significantly affected biodistribution of NMs in subcellular organelles, which contributed to differential biological behaviors of the NMs.