Metal oxide nanoparticle-based magnetic resonance imaging contrast agent with a central cavity
Inventors
Lee, Kwang Yeol • Kim, Min Sik • KIM, Taek Hoon • Vu, Ngoc Phan
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-11324841-B2
Publication Date
2022-05-10
Expiration Date
Abstract
The present invention relates to a magnetic resonance imaging (MRI) contrast agent, particularly an MRI contrast agent derived from nanoparticle that is porous first metal-doped second metal oxide nanoparticle with a central cavity, and a method for producing the same. The MEI contrast agent made in accordance with the present invention can be used not only as a drug-delivery agent for therapy but also as an MRI contrast agent for diagnosis.
Core Innovation
The invention relates to a multifunctional drug delivery-MRI contrast agent derived from porous manganese ion-doped iron oxide nanoparticles having a central cavity. The central cavity has at least one of the shapes selected from octahedral and cross shapes, and the disclosure links the nanoparticle structure to MRI contrast and drug delivery functionality as part of a combined theranostic concept.
The production concept includes synthesizing manganese oxide nanoparticles with a central cavity under an inert gas environment, and forming porous epitaxial layers of iron oxide on the surface of the manganese oxide nanoparticles under the same inert gas environment. The iron oxide layer formation is maintained under a dry air environment to create a porous structure and to enable subsequent manganese removal while preserving the central cavity.
Manganese oxide is removed by treatment with an acidic liquid at high temperature, to form porous manganese ion-doped iron oxide nanoparticles having a central cavity with octahedral and/or cross shapes. The resulting nanoparticles are coated with a biocompatible polymer, including a polymer coating described as pyrenyl polyethylene glycol, to support multifunctional performance.
The disclosure further describes use of the multifunctional nanoparticles for drug loading and release with pH-dependent drug release and includes an example of conjugating the polymer coating with targeting moieties and diagnostic moieties. In the provided context, targeting moieties include antibodies such as anti-HER2/neu, and diagnostic moieties are described in terms of imaging-related components spanning optical, CT, and nonmetallic radioisotopes.
Claims Coverage
The document provides one independent method claim that covers producing a multifunctional drug delivery-MRI contrast agent from porous manganese ion-doped iron oxide nanoparticles with a central cavity shaped as octahedral and/or cross shapes. The inventive features are distributed across the method steps for synthesis, epitaxial iron oxide formation, porous structure development, manganese removal, and biocompatible polymer coating.
Octahedral or cross central cavity manganese oxide nanoparticle synthesis under inert gas
Synthesizing manganese oxide nanoparticles with a central cavity which is at least one of the shapes selected from the group consisting of octahedral and cross shapes under inert gas environment.
Porous epitaxial iron oxide layer formation on manganese oxide under inert gas
Forming porous epitaxial layers of iron oxide on the surface of manganese oxide nanoparticles under inert gas environment.
Porous iron oxide layer formation maintained under dry air
Maintaining the formation of the layer of iron oxide under dry air environment.
High-temperature acidic manganese removal to yield porous Mn-doped iron oxide with central cavity
Removing the manganese oxide by treatment with acidic liquid at high temperature to form a porous manganese ion-doped iron oxide nanoparticles having a central cavity which is at least one of the shapes selected from the group consisting of octahedral and cross shapes.
Biocompatible polymer coating of Mn-doped iron oxide nanoparticles
Coating the nanoparticles with a biocompatible polymer.
Overall claim coverage centers on producing porous manganese ion-doped iron oxide nanoparticles with an octahedral/cross central cavity by combining inert-gas manganese oxide synthesis, porous epitaxial iron oxide formation with dry-air maintenance, high-temperature acidic removal of manganese, and biocompatible polymer coating, to achieve a multifunctional drug delivery-MRI contrast agent.
Stated Advantages
Provides a multifunctional drug delivery-MRI contrast agent derived from porous manganese ion-doped iron oxide nanoparticles with a central cavity.
Supports pH-dependent drug release as described in the disclosure.
Documented Applications
Drug delivery using the multifunctional drug delivery-MRI contrast agent, including drug loading and pH-dependent drug release as described in the disclosure.
Imaging/theranostic functionality using MRI contrast as part of the multifunctional agent, with MR imaging evaluations described in the disclosure.
Targeted association using a polymer conjugated with targeting moieties such as anti-HER2/neu (Herceptin), as described in the disclosure.
Use of diagnostic moieties spanning optical, CT, and nonmetallic radioisotopes as described in the disclosure.
In vivo tumor-related evaluation in tumor-bearing mice as described in the disclosure.
Interested in licensing this patent?