Abstract
Silica nanoparticles (SiNPs) have many physical and chemical characteristics that make it useful tools for different medical and biological applications. However, toxicities and biodistribution of SiNPs after in vivo administration need further investigation, when these materials are used as drug delivery systems (DDS). In this study, surface coating of SiNPs with different densities of polyethylene glycol (PEG) could control their biodistribution and in vivo interaction, especially in different tissue such as blood, tumor, spleen, and liver. In this study, after oral administration, the higher coating density of PEG on the surface of SiNPs (SiNPs_PEGH system) showed prolonged circulation time in the blood compared with lower surface coating density of PEG (SiNPs_PEGL system) or amine surface coating SiNPs (SiNPs_NH2 system). Quantitatively, the SiNPs_NH2 system exhibited 3.5% (dose/ml of serum) after 24 h of the oral administration. While SiNPs_PEGL and SiNPs_PEGH systems showed higher blood retention with 8.3% and 12.6% (dose/ml of serum), respectively. As a result, the accumulation ratio of SiNPs systems in the tumor showed 2.4%, 4.4% and 6% (dose/ml of serum) for SiNPs_NH2, SiNPs_PEGL and SiNPs_PEGH systems, respectively. Both SiNPs_PEGL and SiNPs_PEGH systems showed lower accumulation profiles in the healthy organs such as the liver (6.9% and 6.3% (of dose/gm), respectively), spleen (11.5% and 11% (of dose/gm), respectively), and Peyer’s patches (4.7% and 3.2% (of dose/gm), respectively) compared with SiNPs_NH2 system. Interestingly, the PEG or amine group surface coating could control the biodistribution profiles in tumor site as well as healthy organs differently. Additionally, SiNPs_PEGL and SiNPs_PEGH systems differently induced immune responses based on the PEG surface coating density after oral administration. The anti-PEG immunoglobulin (Ig) M and total IgM antibodies were induced by SiNPs_PEGL and SiNPs_PEGH systems while the SiNPs_NH2 system induced total IgM antibody only. Quantitatively, the induction level of IgM antibody of SiNPs_NH2, SiNPs_PEGL and SiNPs_PEGH systems were 0.82, 0.56 and 0.45 times higher compared to IgM antibody induced by bovine serums albumin (BSA) as a positive control. While the level anti-PEG IgM antibody of SiNPs_PEGL and SiNPs_PEGH systems were 10 and 13.3 times higher compared with that of the SiNPs_NH2 system. Generally, PEG surface coating plays an important role to control the SiNPs-based DDS biodistribution and its immunogenicity. Furthermore, the obtained data from this study can improve the use of SiNPs as DDS for tumor targeting with lower immunogenicity and effective accumulation in the tumor site.
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Acknowledgements
The authors extend their appreciation to the Deputyship for Research & Innovation, Ministry of Education in Saudi Arabia for funding this research work through project number 14/442. Also, the authors would like to extend their appreciation to Taibah University for its supervision support.
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The study was approved by the Animal Care and Use Committee at Department of Zoology, Faculty of Science, Sohag University. All experimental procedures performed were in accordance with ethical standards of Animal Care and Use Committee at Department of Zoology, Faculty of Science, Sohag University.
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Abu-Dief, A.M., Alsehli, M. & Awaad, A. The bioreaction and immune responses of PEG-coated silica NPs and the role of the surface density coating after oral administration into mice. Appl Nanosci 13, 5563–5578 (2023). https://doi.org/10.1007/s13204-023-02770-0
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DOI: https://doi.org/10.1007/s13204-023-02770-0