NDLI: Optimization of micelle-encapsulated extremely small sized iron oxide nanoparticles as a T1 contrast imaging agent: biodistribution and safety profile

Content Provider	Springer Nature : BioMed Central
Author	Suh, Minseok Park, Ji Yong Ko, Guen Bae Kim, Ji Yoon Hwang, Do Won Rees, Louis Conway, Gillian E Doak, Shareen H Kang, Hyelim Lee, Nohyun Hyeon, Taeghwan Lee, Yun-Sang Lee, Dong Soo
Abstract	Background Iron oxide nanoparticles (IONPs) have been cleared by the Food and Drug Administration (FDA) for various clinical applications, such as tumor-targeted imaging, hyperthermia therapy, drug delivery, and live-cell tracking. However, the application of IONPs as T1 contrast agents has been restricted due to their high r2 values and r2/r1 ratios, which limit their effectiveness in T1 contrast enhancement. Notably, IONPs with diameters smaller than 5 nm, referred to as extremely small-sized IONPs (ESIONs), have demonstrated potential in overcoming these limitations. To advance the clinical application of ESIONs as T1 contrast agents, we have refined a scale-up process for micelle encapsulation aimed at improving the hydrophilization of ESIONs, and have carried out comprehensive in vivo biodistribution and preclinical toxicity assessments. Results The optimization of the scale-up micelle-encapsulation process, specifically employing Tween60 at a concentration of 10% v/v, resulted in ESIONs that were uniformly hydrophilized, with an average size of 9.35 nm and a high purification yield. Stability tests showed that these ESIONs maintained consistent size over extended storage periods and dispersed effectively in blood and serum-mimicking environments. Relaxivity measurements indicated an r1 value of 3.43 mM− 1s− 1 and a favorable r2/r1 ratio of 5.36, suggesting their potential as T1 contrast agents. Biodistribution studies revealed that the ESIONs had extended circulation times in the bloodstream and were primarily cleared via the hepatobiliary route, with negligible renal excretion. We monitored blood clearance and organ distribution using positron emission tomography and magnetic resonance imaging (MRI). Additionally, MRI signal variations in a dose-dependent manner highlighted different behaviors at varying ESIONs concentrations, implying that optimal dosages might be specific to the intended imaging application. Preclinical safety evaluations indicated that ESIONs were tolerable in rats at doses up to 25 mg/kg. Conclusions This study effectively optimized a scale-up process for the micelle encapsulation of ESIONs, leading to the production of hydrophilic ESIONs at gram-scale levels. These optimized ESIONs showcased properties conducive to T1 contrast imaging, such as elevated r1 relaxivity and a reduced r2/r1 ratio. Biodistribution study underscored their prolonged bloodstream presence and efficient clearance through the liver and bile, without significant renal involvement. The preclinical toxicity tests affirmed the safety of the ESIONs, supporting their potential use as T1 contrast agent with versatile clinical application.
Related Links	https://jnanobiotechnology.biomedcentral.com/counter/pdf/10.1186/s12951-024-02699-8.pdf
Ending Page	14
Page Count	14
Starting Page	1
File Format	HTM / HTML
ISSN	14773155
DOI	10.1186/s12951-024-02699-8
Journal	Journal of Nanobiotechnology
Issue Number	1
Volume Number	22
Language	English
Publisher	BioMed Central
Publisher Date	2024-07-16
Access Restriction	Open
Subject Keyword	Biotechnology Nanotechnology Molecular Medicine Iron oxide nanoparticle ESIONs Micelle encapsulation MRI T1 contrast
Content Type	Text
Resource Type	Article
Subject	Bioengineering Pharmaceutical Science Medicine Applied Microbiology and Biotechnology Biomedical Engineering Molecular Medicine Nanoscience and Nanotechnology
Journal Impact Factor	10.6/2023
5-Year Journal Impact Factor	11.4/2023

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