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A method for preparing metal nanoclusters, nanoclusters prepared by the method, and contrast agents containing the nanoclusters

A technology of metal nanoclusters and metal salts, which is applied in the field of metal nanoclusters and its preparation, can solve problems such as poor stability, loss, and misjudgment of PET imaging results, and achieve the goals of improving deposition, improving stability, and ensuring accuracy Effect

Active Publication Date: 2019-01-25
INST OF HIGH ENERGY PHYSICS CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, these radioactive metal complexes have two inherent limitations for internal imaging in vivo: first, the complexes formed by radioactive metal nuclides and coupling agents have poor stability in vivo, and these conventional bifunctional chelating agents such as DOTA, NOTA or TETA can bind many different metal ions, resulting in the release of some radioactive metal ions
In addition, many compounds in the body can reduce Cu(II) to Cu(I), causing the loss of Cu, which can complex with proteins in plasma and liver, such as superoxide dismutase (SOD), resulting in the accumulation of Cu in the liver High accumulation; Second, due to the coupling of radioactive metal-coupling agent complexes on the surface of nanoparticles, the surface physicochemical properties of nanoparticles are affected
These two factors could ultimately lead to misinterpretation of PET imaging results

Method used

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  • A method for preparing metal nanoclusters, nanoclusters prepared by the method, and contrast agents containing the nanoclusters
  • A method for preparing metal nanoclusters, nanoclusters prepared by the method, and contrast agents containing the nanoclusters
  • A method for preparing metal nanoclusters, nanoclusters prepared by the method, and contrast agents containing the nanoclusters

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preparation example Construction

[0037]The present invention provides a method for preparing metal nanoclusters, comprising: providing a mixed solution, the mixed solution including a metal salt, a template agent or a template agent containing a disease-targeting ligand; making the mixed solution system undergo redox reaction, to reduce the metal ion contained in the metal salt to a metal atom, and the metal atom acts on the template to form the metal nanocluster; wherein, the template is selected from protein, peptide, polymer or DNA.

[0038] Specifically, the molar ratio of template agent to metal salt is preferably (1-5):(0.1-0.5), more preferably 2:0.3.

[0039] Preferably, by adding a strong base or a reducing agent to the mixed liquid, the mixed liquid system can undergo a redox reaction, the strong base can be a water-soluble strong base, such as NaOH or KOH, and the reducing agent Can be NaBH 4 .

[0040] The metal salt may include radioactive metal ions and non-radioactive metal ions, the radioac...

Embodiment 1

[0056] Embodiment 1, the preparation of Cu nanocluster

[0057] 1mL, 20mM CuCl 2 Mix the solution with 5mL, 40mg / mL BSA or 5mL, 42mg / mL BSA-LHRH protein solution, stir at room temperature for 2-3min, add 0.4mL, 0.5M NaOH solution to adjust the pH value to 12, the color of the solution changes from blue to purple , the formed solution continued to be stirred at 55° C. for 5 h, and the synthesized Cu nanoclusters were ultrafiltered with an ultrafiltration tube with a cutoff of 3000 to remove free metal ions. The synthesized Cu nanoclusters are represented as: Cu NC @BSA, Cu NC @BSA-LHRH. Cu NC @BSA and Cu NC @BSA-LHRH fluoresces purple under visible light and blue under UV light.

[0058] like Figure 1a As shown, HRTEM shows that the synthesized nanoclusters have an ultra-small particle size and good dispersion, with a particle size of about 3nm. Figure 1b The indicated particle size, as determined by DLS, is approximately 3.5 nm. Figure 1c The shown UV and fluorescen...

Embodiment 2

[0063] Embodiment 2, radioactive [ 64 Preparation of Cu]Cu Nanoclusters

[0064] Will 64 CuCl 2 (555 millibeck (MBq), 80 μL) with 920 μL, 20 mM CuCl 2 The solutions are mixed to produce a metal salt solution. Mix 5mL, 40mg / mL BSA or 5mL, 42mg / mL BSA-LHRH protein solution with the above metal salt solution, stir at room temperature for 2-3min, add 0.4mL, 0.5M NaOH solution to adjust the pH value of the above mixture to 12, The color of the mixed solution changed from blue to purple, and the formed solution was stirred at 55°C for 5h to obtain [ 64 Cu]Cu nanoclusters. Finally, the synthesized [ 64 Cu]Cu nanoclusters were ultrafiltered with an ultrafiltration tube with a cutoff of 3000 to remove free metal ions. Synthetic[ 64 Cu]Cu nanoclusters are expressed as: [ 64 Cu]Cu NC @BSA, [ 64 Cu]Cu NC @BSA-LHRH. After compositing ends, [ 64 Cu]Cu NC @BSA and [ 64 Cu]Cu NC The radiolabeling efficiencies of @BSA-LHRH all reached above 95%.

[0065] The synthesized [ 64...

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Abstract

The invention provides a preparation method of a metal nanocluster. The preparation method comprises: providing a mixed solution, wherein the mixed solution comprises a metal salt, a template agent or a template agent containing a disease targeting ligand; and enabling the mixed solution system to undergo redox reaction to reduce metal ions contained in the metal salt into metal atoms, and enabling the metal atoms to act on the template agent to form the metal nanocluster, wherein the template agent is selected from proteins, peptides, polymers or DNA. When being used for PET imaging, the metal nanocluster provided by the invention has various advantages that the radiolabelling stability is greatly improved, and the diagnosis precision is ensured; due to the super-small particle size of the nanocluster and a water-soluble peptide shell, the nanocluster has some superior characteristics; and using a macrocyclic coupling agent for coupling radioactive metal ions is avoided due to the existence of a template, and the template can be used for coupling functional molecules such as small peptides and small molecules targeting diseases.

Description

technical field [0001] The invention relates to a metal nanocluster and a preparation method thereof, in particular to a metal nanocluster that can be used in the field of disease-targeted PET / SPECT imaging and a preparation method thereof. Background technique [0002] PET / SPECT (Positron Emission Tomography / Single Photon Emission Computed Tomography) imaging is widely used in the diagnosis of tumors due to its high detection sensitivity, unlimited tissue penetration and quantitative analysis of the whole image. , assessment of staging and treatment, and diagnosis of neurodegenerative diseases and cardiovascular and cerebrovascular diseases. [0003] Currently,[ 18 F]-deoxyglucose (FDG) is the only PET radiocontrast agent routinely evaluated clinically, mainly for tumor imaging. Although the use of FDG as a radiocontrast agent to assess tissue metabolism provides a useful imaging tool for tumors, FDG is relatively nonspecific and less useful for imaging tumors with very l...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K51/00A61K51/08A61K49/00B22F9/24
Inventor 高学云高福平
Owner INST OF HIGH ENERGY PHYSICS CHINESE ACAD OF SCI