Silica encapsulation of ZnO nanoparticles reduces their toxicity for cumulus cell-oocyte-complex expansion

Antonella Camaioni, Micol Massimiani, Valentina Lacconi, Andrea Magrini, Antonietta Salustri, Georgios A. Sotiriou, Dilpreet Singh, Dimitrios Bitounis, Beatrice Bocca, Anna Pino, Flavia Barone, Valentina Prota, Ivo Iavicoli, Manuel Scimeca, Elena Bonanno, Flemming R. Cassee, Philip Demokritou, Antonio Pietroiusti, Luisa Campagnolo

Research output: Contribution to journalArticlepeer-review


Background: Metal oxide nanoparticles (NPs) are increasingly used in many industrial and biomedical applications, hence their impact on occupational and public health has become a concern. In recent years, interest on the effect that exposure to NPs may exert on human reproduction has grown, however data are still scant. In the present work, we investigated whether different metal oxide NPs interfere with mouse cumulus cell-oocyte complex (COC) expansion. Methods: Mouse COCs from pre-ovulatory follicles were cultured in vitro in the presence of various concentrations of two types of TiO2 NPs (JRC NM-103 and NM-104) and four types of ZnO NPs (JRC NM-110, NM-111, and in-house prepared uncoated and SiO2-coated NPs) and the organization of a muco-elastic extracellular matrix by cumulus cells during the process named cumulus expansion was investigated. Results: We show that COC expansion was not affected by the presence of both types of TiO2 NPs at all tested doses, while ZnO NM-110 and NM-111 induced strong toxicity and inhibited COCs expansion at relatively low concentration. Medium conditioned by these NPs showed lower toxicity, suggesting that, beside ion release, inhibition of COC expansion also depends on NPs per se. To further elucidate this, we compared COC expansion in the presence of uncoated or SiO2-coated NPs. Differently from the uncoated NPs, SiO2-coated NPs underwent slower dissolution, were not internalized by the cells, and showed an overall lower toxicity. Gene expression analysis demonstrated that ZnO NPs, but not SiO2-coated ZnO NPs, affected the expression of genes fundamental for COC expansion. Dosimetry analysis revealed that the delivered-to-cell mass fractions for both NPs was very low. Conclusions: Altogether, these results suggest that chemical composition, dissolution, and cell internalization are all responsible for the adverse effects of the tested NPs and support the importance of a tailored, safer-by-design production of NPs to reduce toxicity.

Original languageEnglish (US)
Article number33
JournalParticle and Fibre Toxicology
Issue number1
StatePublished - Dec 2021
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Toxicology
  • Health, Toxicology and Mutagenesis


  • Cumulus cells
  • Cumulus expansion
  • Extracellular matrix
  • Oocyte
  • Silica
  • Titanium dioxide nanoparticles
  • Zinc oxide nanoparticles


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