Octapod iron oxide nanoparticles as high performance T2 contrast agents for magnetic resonance imaging
Inventors
Gao, Jinhao • Chen, Xiaoyuan • Zhao, Zenghuan
Assignees
Xiamen University • US Department of Health and Human Services
Publication Number
US-9974868-B2
Publication Date
2018-05-22
Expiration Date
2033-06-03
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Abstract
Disclosed are nanoparticles comprising octapod iron oxide having eight trigonal bipyramidal arms and a method of preparing the same. The nanoparticles are prepared by heating a mixture of a ferric carboxylate, a carboxylic acid, a chloride salt, water, and a non-polar solvent, to a temperature above about 300° C. Also disclosed is a method of magnetic resonance imaging a tissue in a mammal, comprising use of the aforesaid nanoparticles.
Core Innovation
The invention provides nanoparticles comprising octapod iron oxide having eight trigonal bipyramidal arms. These nanoparticles are characterized by a concave polyhedral geometry bounded by (311) high-index facets, 14 facets in total, and 24 edges. The octapod iron oxide consists of magnetite and chloride ions, where the chloride ions are chelated to Fe(III) ions exposed on the (311) facets. The nanoparticles exhibit ultrahigh transverse relaxivity (r2) values, significantly higher than spherical iron oxide nanoparticles of comparable volume, making them highly effective T2 contrast agents for magnetic resonance imaging (MRI).
The method of preparing these octapod iron oxide nanoparticles involves heating a mixture of a ferric carboxylate, a carboxylic acid, a chloride salt, water, and a non-polar solvent to a temperature above about 300° C., followed by isolating the nanoparticles. The chloride ions play a critical role in directing the formation of the unique octapod structure, likely by selectively binding to iron ions on high-index facets during nanoparticle growth. The nanoparticles can be encapsulated with agents such as HDA-G2 to facilitate dispersion in aqueous media and functionalization with targeting ligands.
The background identifies a problem with existing T2 contrast agents used in MRI, such as Feridex™ and Resovist™, which have poor crystallinity and relatively low relaxivity, limiting MRI sensitivity and diagnostic accuracy. These agents can also cause false-positive diagnoses due to hypointense areas unrelated to pathology. Thus, there existed an unmet need for new T2 contrast agents with higher relaxivity for enhanced MRI performance. The invention addresses this need by providing octapod iron oxide nanoparticles with significantly improved relaxivity and contrast capability.
Claims Coverage
The patent includes two independent claims focused on isolated nanoparticles comprising octapod iron oxide with defined structure and a method of preparing such nanoparticles.
Nanoparticles comprising octapod iron oxide with defined structure
Isolated nanoparticles consisting of magnetite and chloride ions, shaped as eight trigonal bipyramidal arms forming a concave polyhedral geometry bounded by (311) high-index facets with 14 facets and 24 edges. Chloride ions are chelated to Fe(III) ions on the (311) facets.
Method for preparing octapod iron oxide nanoparticles
Heating a mixture of a ferric carboxylate, a carboxylic acid, a chloride salt, water, and a non-polar solvent to above about 300° C. and isolating the nanoparticles. The process produces octapod iron oxide nanoparticles with the described structure and composition.
The independent claims cover both the novel octapod iron oxide nanoparticles characterized by their unique geometry and chloride ion coordination, and a method for synthesizing such nanoparticles by thermal treatment of a specific mixture. The claims also encompass encapsulated forms and their use as MRI contrast agents.
Stated Advantages
Octapod iron oxide nanoparticles exhibit ultrahigh transverse relaxivity (r2) values, approximately 5.4 times greater than spherical nanoparticles of similar volume, enabling highly sensitive T2 MRI contrast enhancement.
The unique octapod morphology significantly increases the effective magnetic core radius and local field inhomogeneity, resulting in improved MRI performance and small tumor detection capability.
The nanoparticles demonstrate superparamagnetic behavior at room temperature, biocompatibility with no appreciable cytotoxicity, excellent colloidal stability in aqueous media, and surface functionalization potential via encapsulating agents.
Higher MRI contrast can be achieved at reduced doses compared to conventional spherical iron oxide nanoparticles, potentially lowering cost and side effects in clinical diagnosis.
Documented Applications
Use as T2 contrast agents in magnetic resonance imaging for molecular imaging and clinical diagnosis, particularly for detection of lesions and tumors with enhanced sensitivity.
Imaging of various tissues in mammals, specifically liver tissue and liver cancer tissue, using the nanoparticles administered intravenously.
Contrast agents for MRI, X-ray CT, ultrasound imaging, and scintigraphy, with preferred use in MRI.
Encapsulated nanoparticles conjugated with targeting ligands for selective imaging of pathological cells via specific surface receptors.
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