Intracellular processing of silica-coated superparamagnetic iron nanoparticles in human mesenchymal stem cells

Harrison, Richard P.; Chauhan, Veeren M.; Onion, David; Aylott, Jonathan W.; Sottile, Virginie

Abstract

Silica-coated Superparamagnetic Iron Nanoparticles (SiMAGs) are an exciting biomedical technology capable of targeted delivery of cell-based therapeutics and disease diagnosis. However, in order to realise their full clinical potential, their intracellular fate must be determined. The analytical techniques of super-resolution fluorescence microscopy, particle counting flow cytometry and pH-sensitive nanosensors were applied to elucidate mechanisms of intracellular SiMAG processing in human mesenchymal stem cell (hMSCs). Super-resolution microscopy showed SiMAG fluorescently-tagged nanoparticles are endocytosed and co-localised within lysosomes. When exposed simulated lysosomal conditions SiMAGs were solubilised and exhibited diminishing fluorescence emission over 7 days. The in vitro intracellular metabolism of SiMAGs was monitored in hMSCs using flow cytometry and co-localised pH-sensitive nanosensors. A decrease in SiMAG fluorescence emission, which corresponded to a decrease in lysosomal pH was observed, mirroring ex vivo observations, suggesting SiMAG lysosomal exposure degrades fluorescent silica-coatings and iron cores. These findings indicate although there is a significant decrease intracellular SiMAG loading, sufficient particles remain internalised (>50%) to render SiMAG treated cells amenable to long-term magnetic cell manipulation. Our analytical approach provides important insights into the understanding of the intracellular fate of SiMAG processing, which could be readily applied to other particle therapeutics, to advance their clinical translation.

Citation

Harrison, R. P., Chauhan, V. M., Onion, D., Aylott, J. W., & Sottile, V. (2019). Intracellular processing of silica-coated superparamagnetic iron nanoparticles in human mesenchymal stem cells. RSC Advances, 9(6), 3176-3184. https://doi.org/10.1039/C8RA09089K

• Journal Article Type: Article
• Acceptance Date: Dec 21, 2018
• Publication Date: Jan 23, 2019
• Deposit Date: Jan 23, 2019
• Publicly Available Date: Jan 24, 2019
• Journal: RSC Advances
• Electronic ISSN: 2046-2069
• Publisher: Royal Society of Chemistry
• Peer Reviewed: Peer Reviewed
• Volume: 9
• Issue: 6
• Pages: 3176-3184
• DOI: https://doi.org/10.1039/C8RA09089K
• Public URL: https://nottingham-repository.worktribe.com/output/1479582
• Publisher URL: https://pubs.rsc.org/en/Content/ArticleLanding/2019/RA/C8RA09089K#!divAbstract
• Additional Information: : This document is Similarity Check deposited; : Supplementary Information; : Veeren M. Chauhan (ORCID); : Virginie Sottile (ORCID); : Single-blind; : Received 2 November 2018; Accepted 21 December 2018; Version of Record published 23 January 2019
• Contract Date: Jan 24, 2019