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Kidney-targeted near-infrared fluorescent probe and its preparation method and application

A near-infrared and luminescent probe technology, applied in the field of fluorescent probes and their preparation, can solve the problems of imaging diagnosis or targeted drug delivery instability, short residence time of probes, fluctuations in fluorescent signals, etc.

Active Publication Date: 2022-05-20
FUDAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, in renal fluorescence imaging based on the renal clearance pathway, the probe stays in the kidney for a short time, and the fluorescent signal will fluctuate with urination, resulting in instability in imaging diagnosis or targeted drug delivery.
Therefore, it remains a challenge to develop probes capable of targeting the kidney for prolonged periods of time for renal fluorescence imaging.

Method used

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  • Kidney-targeted near-infrared fluorescent probe and its preparation method and application
  • Kidney-targeted near-infrared fluorescent probe and its preparation method and application
  • Kidney-targeted near-infrared fluorescent probe and its preparation method and application

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Experimental program
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Effect test

Embodiment 1

[0031] Weigh 20 mg of ICG-COOH into a round-bottomed flask, add 6 mL of dichloromethane to dissolve, then add 15 mg of EDC and 15 mg of NHS, and stir the above reaction solution at room temperature in the dark for 24 h. Subsequently, the reaction solvent was dried by vacuum rotary evaporation to obtain the activated ICG mixture. The above mixture was separated by silica gel column chromatography to obtain the pure product of activated ICG. Weigh 3 mg of the activated product above and dissolve it in 3 mL of dimethylformamide, add 10 mg of triethylamine to adjust the pH of the solution to 8-9, then add 7 mg of KTP1, and place the above reaction in the dark and stir at room temperature for 12 h, The ICG-KTP1 kidney targeting probe mixture was obtained. The solvent dimethylformamide was removed by vacuum rotary evaporation, and the obtained solid powder was redispersed with dichloromethane to obtain a suspension. The supernatant was discarded and the precipitate was washed with ...

Embodiment 2

[0033] Weigh 10 mg of FD1080 into a round bottom flask, add 4 mL of dichloromethane to dissolve, then add 5 mg of EDC and 5 mg of NHS, and place the above reaction solution at room temperature and stir for 12 h in the dark. Subsequently, the reaction solvent was dried by vacuum rotary evaporation to obtain the activated FD1080 mixture. The above mixture was separated by silica gel column chromatography to obtain the pure product of activated FD1080. Weigh and dissolve 2 mg of the activated product above in 2 mL of methanol, add 10 mg of triethylamine to adjust the pH of the solution to 8-9, then add 5 mg of KTP2, and place the above reaction in the dark and stir at room temperature for 12 h to obtain FD1080 - KTP2 kidney targeting probe mix. The solvent methanol was removed by vacuum rotary evaporation, and the obtained solid powder was redispersed with ethyl acetate to obtain a suspension. The supernatant was discarded and the precipitate was washed with ethyl acetate for 3 ...

Embodiment 3

[0035]Weigh gold nanoparticles GNP (particle size 2.5 nm, 3 mg) into a glass bottle, add 5 mL of deionized water to dissolve, then add 5 mg of KTP1 polypeptide, put the above reaction bottle in a water bath at 45 degrees Celsius, and stir for 18 h, Kidney-targeting peptide-coupled gold nanoparticles. The above product was placed in a rotary evaporator to remove water to obtain GNP-KTP1 fluorescent probe powder. The above products were separated by Sephadex G25 chromatographic column to obtain the purified kidney targeting probe GNP-KTP1.

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Abstract

The invention belongs to the technical field of biomaterials, in particular to a kidney-targeting near-infrared luminescent probe and its preparation method and application. The near-infrared luminescent probe of the present invention is composed of a kidney-targeting polypeptide covalently linked to a luminescent material; residues (including amino, carboxyl, or thiol) of the amino acid side chain of the polypeptide form chemical bonds with fluorescent molecules; the polypeptide is used to enhance the fluorescence of fluorescent molecules. Water soluble and targets tubular structures in the kidney; fluorescent molecule for fluorescence imaging. The kidney-targeting probe of the present invention has high specificity for kidney targeting, more than 70% of the injected dose of the probe is enriched in the kidney, and the targeted residence time of the kidney-targeting probe in the kidney is greater than 48 h, which can be used as a specific It is a kidney-targeted fluorescent imaging agent, which can be used for the diagnosis of early renal injury status and the targeted delivery of therapeutic drugs for renal diseases.

Description

technical field [0001] The invention belongs to the technical field of biomaterials, and in particular relates to a kidney-targeting fluorescent probe and its preparation method and application. Background technique [0002] Kidney disease is usually asymptomatic in the early stages, but with the development of kidney disease, it may eventually lead to severe renal failure. Nearly 10% of adults worldwide suffer from early asymptomatic kidney disease, which causes about 2 million deaths each year from late kidney failure. The current clinical diagnostic methods for kidney diseases rely on the determination of blood urea nitrogen (BUN) and serum creatinine (sCr). These clinical examination markers remain within the normal range until GFR is lost and therefore cannot be used for early renal injury detection. Non-invasive intravital imaging techniques such as single photon emission computed tomography (SPECT), magnetic resonance imaging (MRI), and positron emission tomography / ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K49/00
CPCA61K49/0056A61K49/0019A61K49/0034A61K49/0021
Inventor 张凡陈莹
Owner FUDAN UNIV