A preparation method of 64cu-labeled folic acid-targeted functionalized polyethyleneimine stabilized trimanganese tetraoxide nanoparticles

A technology of trimanganese tetraoxide nanometer and polyethyleneimine, which is applied in the field of preparation of trimanganese tetraoxide nanoparticle, can solve the problems of short cycle time, expensive MR imaging technology, long scanning time, etc., and achieve good stability, The effect of good stability and biocompatibility

Inactive Publication Date: 2019-03-08
DONGHUA UNIV +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, various imaging techniques have advantages and disadvantages. For example, MR imaging has high resolution, no radioactive radiation, and can obtain anatomical and physiological information at the same time, but MR imaging techniques are expensive and take a long time to scan.
PET imaging has high sensitivity and the function of whole-body imaging, but the nuclide required for PET examination has certain radioactivity, and the half-life of the nuclide is relatively short, and the circulation time in the body is short

Method used

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  • A preparation method of 64cu-labeled folic acid-targeted functionalized polyethyleneimine stabilized trimanganese tetraoxide nanoparticles
  • A preparation method of 64cu-labeled folic acid-targeted functionalized polyethyleneimine stabilized trimanganese tetraoxide nanoparticles
  • A preparation method of 64cu-labeled folic acid-targeted functionalized polyethyleneimine stabilized trimanganese tetraoxide nanoparticles

Examples

Experimental program
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Effect test

Embodiment 1

[0057] (1) Dissolve FA with a dry weight of 44.14 mg in 5 mL of DMSO, and add EDC with a dry weight of 19.17 mg dissolved in 2 mL of DMSO solution dropwise while stirring. After stirring for 3 hours, add 100 mg dry weight NH dissolved in 5 mL DMSO solution 2 -PEG-COOH (Mw=2000), wherein FA and NH 2 -The molar ratio of PEG-COOH is 2:1, the molar ratio of EDC and FA is 1:1, react for 1 day, and dialyze the resulting solution with cellulose dialysis membrane MWCO=1000 in phosphate buffer solution and distilled water for 3 days , freeze-dried to obtain FA-PEG-COOH.

[0058] (2) Dissolve 100mg of PEI in 15mL of diethylene glycol, then add 250mg of manganese acetylacetonate into the solution of PEI in diethylene glycol, disperse evenly and stir for 1h under air atmosphere, then transfer it to the autoclave In the process, the reaction was carried out at a high temperature of 180°C and a high pressure of 0.2MPa for 24h. After cooling, remove the large particle precipitate at the b...

Embodiment 2

[0061] During the synthesis process, the FA-PEG-COOH obtained in Example 1 was characterized by proton nuclear magnetic resonance, and the results showed that 0.5 FA ( figure 2 ).

[0062] During the synthesis process, the functionalized trimanganese tetraoxide nanoparticles obtained in Example 1 were characterized by infrared spectroscopy, and the FTIR test results showed that: Mn 3 o 4 -2950cm on PEI NPs -1 with 2850cm -1 The peak at is attributed to the stretching vibration peak of methylene on PEI, which is consistent with the characteristic peak at this place on PEI. Also, 1459-1642cm on PEI -1 and 1140cm -1 The peaks at are assigned to the stretching vibration of C=O and the stretching vibration of C-O respectively. In Mn 3 o 4 Consistent characteristic peaks can be found in the infrared spectra of -PEI NPs. in Mn 3 o 4 -636cm on the infrared spectrum of PEI NPs -1 The peak at is Mn 3 o 4 On the Mn-O stretching vibration peak, but this characteristic peak w...

Embodiment 3

[0075] Detect the in vitro biocompatibility of the prepared functionalized trimanganese tetraoxide nanocarrier with MTT test, take the carrier material NOTA-Mn in Example 1 3 o 4 -PEI-Ac-FI-(PEG-FA) NPs and the control material NOTA-Mn in Comparative Example 1 3 o 4 -PEI-Ac-FI-(mPEG)NPs were dissolved in PBS buffer to prepare a solution with a Mn concentration of 1000 μg / mL, and then diluted to a concentration of 500 μg / mL, 250 μg / mL, 100 μg / mL, and 50 μg / mL The solution. After incubating HeLa cells with the above-mentioned Example 1 material and Comparative Example 1 material with different Mn concentrations (the respective final concentrations are 100 μg / mL, 50 μg / mL, 25 μg / mL, 10 μg / mL, 5 μg / mL) for 24 h, the Pour off the material, add 180 μL of medium and 20 μL of MTT, incubate at 37°C for 4 hours, pour out the culture medium, add 200 μL of DMSO, shake on a shaker for 20 minutes, measure the results with a microplate reader, and get Figure 8 Shown data, the result sho...

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Abstract

The invention relates to a method for preparing 64 Cu marked and folic acid targeted functional trimanganese tetroxide nano-particles with stable polyethyleneimine.The method comprises the steps that folic acid is mixed with NH2-PEG-COOH to obtain FA-PEG-COOH; manganese tris(4-oxopent-2-en-2-oate) is in reaction with PEI to obtain Mn3O4-PEI NPs, FI modification is performed, NOTA-NHS and activated FA-PEG-COOH are added, acetylation is performed, and MOTA-Mn3O4-PEI-Ac-FI-(PEG-FA)NPs is obtained; ammonium acetate is in reaction with [64 Cu]CuCl2 and added to an NOTA-Mn3O4-PEI-Ac-FI-(PEG-FA)NPs solution then, and the nano-particles are obtained after reaction.According to the method, the preparation process is simple and easy to operate; the obtained material has an excellent PET / MR double modal imaging effect, and the method has a potential application value in the multimodal nano contrast agent field.

Description

technical field [0001] The invention belongs to the field of preparation of functional polyacetylimide materials, in particular to a 64 Preparation of Cu-labeled folic acid-targeted functionalized polyethyleneimine-stabilized trimanganese tetraoxide nanoparticles. Background technique [0002] Cancer is an abnormal lesion formed by the body under the action of various carcinogenic factors, the cells of local tissues lose the normal regulation of their growth at the gene level, resulting in abnormal clonal proliferation. The treatment effect and cost of cancer are closely related to the period of cancer discovery, so early detection and early treatment are the most effective ways to reduce cancer mortality. Molecular imaging is the application of molecular biology nanotechnology and imaging methods to detect abnormalities at the molecular level of diseased cell nuclei in the early stages of tumors before clinical symptoms appear, so as to achieve early diagnosis of tumors. ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K51/06A61K51/12
CPCA61K51/065A61K51/1244
Inventor 史向阳朱静怡陈凯李洪生
Owner DONGHUA UNIV
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