Tumor-targeted magnetic resonance imaging and fluorescent supermolecular imaging contrast agent and preparation and application thereof

A nuclear magnetic resonance and tumor targeting technology, applied in the field of imaging diagnosis, can solve the problems of lack of tumor targeting and easy aggregation of probes, and achieve excellent fluorescence performance, high relaxation rate, and improved specificity and sensitivity. Effect

Inactive Publication Date: 2018-05-25
DALIAN INST OF CHEM PHYSICS CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the probe has a hydrated particle size of 32nm, is prone to aggregation, and the probe lacks tumor targeting

Method used

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  • Tumor-targeted magnetic resonance imaging and fluorescent supermolecular imaging contrast agent and preparation and application thereof
  • Tumor-targeted magnetic resonance imaging and fluorescent supermolecular imaging contrast agent and preparation and application thereof
  • Tumor-targeted magnetic resonance imaging and fluorescent supermolecular imaging contrast agent and preparation and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0056] Preparation of contrast agents for tumor-targeted nuclear magnetic resonance and near-infrared fluorescence supramolecular imaging:

[0057] (1) Preparation of hydrophilic polymer framework material: Add 0.1013g of hyaluronic acid (HA) into 10mL of deionized water, and add 0.0095g of 1-ethyl-(3-dimethylaminopropyl)carbodiimide Hydrochloride (EDC.HCL) and 0.0059g N-hydroxysuccinimide (NHS) were activated for 30 minutes, 0.0147g ethylenediamine-β-cyclodextrin was added, and the reaction was carried out at room temperature for 24 hours. Then add it into a 500Da dialysis bag, dialyze in deionized water for 48 hours, and freeze-dry to obtain a hydrophilic polymer framework material.

[0058] (2) Preparation of NMR ligand molecule: Dissolve 0.1018g of tri-tert-butyl 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) in 10mL di Chloromethane (DCM), and 0.026g N-hydroxysuccinimide (NHS) were activated at room temperature under the action of 0.1861g dicyclohexylcar...

Embodiment 2

[0062] Preparation of contrast agents for tumor-targeted nuclear magnetic resonance and near-infrared fluorescence supramolecular imaging:

[0063] (1) Preparation of hydrophilic polymer framework material: Take 0.100 g of hyaluronic acid (HA) and add it to 10 mL of deionized water, add 0.0198 g of 1-ethyl-(3-dimethylaminopropyl) carbodiimide Hydrochloride (EDC.HCL) and 0.0115g N-hydroxysuccinimide (NHS) were activated for 30 minutes, 0.0294g ethylenediamino-β-cyclodextrin was added, and the reaction was carried out at room temperature for 24 hours. Then add it into a 500Da dialysis bag, dialyze in deionized water for 48 hours, and freeze-dry to obtain a hydrophilic polymer framework material.

[0064] (2) Preparation of NMR ligand molecule: Dissolve 0.1018g of tri-tert-butyl 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) in 10mL di Chloromethane (DCM), and 0.026g N-hydroxysuccinimide (NHS) were activated at room temperature under the action of 0.1861g dicycl...

Embodiment 3

[0068] Preparation of tumor-targeted nuclear magnetic resonance and near-infrared fluorescence dual-mode imaging contrast agent:

[0069](1) Preparation of hydrophilic polymer framework material: Add 0.1009g of hyaluronic acid (HA) into 10mL of deionized water, and add 0.0389g of 1-ethyl-(3-dimethylaminopropyl)carbodiimide Hydrochloride (EDC.HCL) and 0.0231g N-hydroxysuccinimide (NHS) were activated for 30 minutes, 0.0583g ethylenediamine-β-cyclodextrin was added, and the reaction was carried out at room temperature for 24 hours. Then add it into a 500Da dialysis bag, dialyze in deionized water for 48 hours, and freeze-dry to obtain a hydrophilic polymer framework material.

[0070] (2) Preparation of NMR ligand molecule: Dissolve 0.1018g of tri-tert-butyl 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) in 10mL di Chloromethane (DCM), and 0.026g N-hydroxysuccinimide (NHS) were activated at room temperature under the action of 0.1861g dicyclohexylcarbodiimide (...

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Abstract

The invention discloses a tumor-targeted magnetic resonance imaging and fluorescent supermolecular imaging contrast agent and preparation and application thereof. The tumor-targeted magnetic resonanceimaging and fluorescent supermolecular imaging contrast agent is characterized in that a water-soluble macromolecular skeleton material is modified by molecules with a specific binding function, andis self-assembled with corresponding ligand molecules to form supermolecular nanoparticles under the mutual action of a host and a guest, and the ligand molecules are modified with a paramagnetism material with an imaging function and a near-infrared fluorescent dye. The tumor-targeted magnetic resonance imaging and fluorescent supermolecular imaging contrast agent has the advantages that the tumor cells of a receptor with high expression specificity can be targeted; the magnetic resonance imaging and fluorescent double imaging functions are realized; the contrast agent can be used for the in-operation fluorescent guidance positioning and the post-operation magnetic resonance monitoring in the tumor cutting operation.

Description

technical field [0001] The invention relates to the field of imaging diagnosis, in particular to a tumor-targeted self-assembled nuclear magnetic resonance-fluorescence dual-mode supramolecular imaging contrast agent and its preparation method, and its use in tumor resection surgery for fluorescence-guided positioning and postoperative nuclear magnetic resonance applications in monitoring. Background technique [0002] In the early stage of cancer, if the physiological and morphological changes of diseased organs or tissues can be detected quickly and accurately, and corresponding imaging information can be given, it is of great significance for the early diagnosis of cancer. Contrast agents are such substances that are injected into specific tissues or organs of the human body to produce density or other differences from normal tissue parts and visualize these differences, thereby providing important clinical information about diseases. [0003] MRI (Magnetic Resonance ima...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K49/18A61K49/12A61K49/00
CPCA61K49/0002A61K49/0054A61K49/0093A61K49/085A61K49/12A61K49/1824
Inventor 孙广炜王辉辉刘洋张英赵珊
Owner DALIAN INST OF CHEM PHYSICS CHINESE ACAD OF SCI
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