Comparative Toxicity of PEG and Folate-Derived Blue-Emitting Silicon Nanoparticles: In Vitro and In Vivo Studies

Abstract

Aim: Amino functionalization is a first step modification aiming to achieve biomedical applications of silicon nanoparticles, for example, for photodynamic therapy or radiotherapy. Nevertheless, toxicity and low quantum yields due to the positive charge of amino groups emerge as a problem that could be solved with subsequent derivatizations. Materials & methods: Folic and PEG-conjugated nanoparticles were obtained from amino-functionalized silicon nanoparticle (NH₂SiNP). Cytotoxicity was determined on a tumor cell line at low and high concentrations. Four end points of in vivo toxicity were evaluated on zebrafish (Danio rerio). Results: Folic acid functionalization reduced the cytotoxicity in comparison to amino and PEG-functionalized nanoparticles. In zebrafish, folic functionalization lowered toxicity in general while PEG increased it. Conclusion: Functionalization of NH₂SiNP with folic acid reduced the toxic effects in vitro and in vivo. This could be useful for therapeutic applications. PEG functionalization did not lower the toxicity.

Keywords::

• folic acid
• silicon nanoparticles
• zebrafish

Author contributions

MN Calienni performed toxicity determinations in zebrafish model. She also designed experiments, interpreted results, contributed to first outline and subsequent drafts and approved the final version of the manuscript. CR Lillo synthesized and characterized the nanoparticles, designed experiments, contributed to first outline and subsequent drafts, and approved the final version of the manuscript. MJ Prieto took part in the experimental design of the toxicity determinations on zebrafish, interpreted results, contributed to first outline and subsequent drafts, and approved the final version of the manuscript. RM Gorojod performed together with CR Lillo the cytotoxicity determinations on C6 cells, interpreted results, contributed to first outline and subsequent drafts, and approved the final version of the manuscript. SV Alonso is the director of the Laboratory of Biomembranes in which zebrafish determinations took place and is PhD co-advisor of MN Calienni. She contributed to first outline and subsequent drafts, and approved the final version of the manuscript. ML Kotler was the doctoral thesis co-director (PhD co-advisor) of CR Lillo and performed radiotherapy assays. She is the director of the laboratory in which took place the experiments on C6 cells; is a director and PhD advisor to RM Gorojod; contributed to first outline and subsequent drafts, and approved the final version of the manuscript. MC González was the doctoral thesis director (PhD advisor) to CR Lillo. She designed experiments and conducted the work of CR Lillo. She interpreted results; contributed to first outline and subsequent drafts, and approved the final version of the manuscript. J Montanari is the director of the research line of nanosystems for biomedical applications in which MN Calenni develops her PhD studies. He is PhD advisor to MN Calienni. He designed experiments and conducted the work of CR Lillo and MN Calienni, interpreted results, contributed to first outline and subsequent drafts, and approved the final version of the manuscript.

Financial & competing interests disclosure

MC González, ML Kotler, SV Alonso, MJ Prieto and J Montanari are members of CONICET (National Council of Science and Technology Research in Argentina). CR Lillo, MN Calienni and RM Gorojod also have been granted with fellowships from CONICET. Grants received from UNQ (National University of Quilmes), CONICET (PIP 0358, 2014/2016) and MINCyT (Ministery of Science and Technology of Argentina).

Ethical disclosure

All animal procedures were performed in strict accordance with International Guidelines for animal care and maintenance. The protocols were approved by the Institutional Committee for the Care and Use of Laboratory Animals and the Ethic Committee of the National University of Quilmes (CE-UNQ 2/2014, CICUAL-UNQ 013-15 and CICUAL-UNQ 014-15; Buenos Aires, Argentina). All institutional and national guidelines for the care and use of laboratory animals were followed.

Additional information

Funding

MC González, ML Kotler, SV Alonso, MJ Prieto and J Montanari are members of CONICET (National Council of Science and Technology Research in Argentina). CR Lillo, MN Calienni and RM Gorojod also have been granted with fellowships from CONICET. Grants received from UNQ (National University of Quilmes), CONICET (PIP 0358, 2014/2016) and MINCyT (Ministery of Science and Technology of Argentina).