Near-infrared second window emitted micro-molecular rear earth complex fluorescence probe and preparation method thereof

A technology of rare earth complexes and fluorescent probes, applied in the field of small molecule rare earth complex fluorescent probes and its preparation, can solve problems such as emission peak width, slow metabolism, and limited application value

Pending Publication Date: 2018-06-12
FUDAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

This technology allows for chemical modification or binding between certain molecules that are involved with specific functions within cells called macrocystins (a type of organic compound). These modified structures have been found effective at deliver drugs into cancerous tissues through their interactions with other proteins like histones lining up DNA) by modifying them's interaction capabilities rather than directly interacting with these targets themselves.

Problems solved by technology

This patents describes different types of probes called fluoresceins or phospholipid nanocomplexes that help study cancer cells better than other organs like kidney stones. These probes emit signals at specific frequencies when excited by laser radiation, making them useful tools for medical purposes. However, they still suffer from certain drawbacks including limited biocompatibility, difficulty dissolving during use, lack of selectivity towards particular targets, short lifetimes, and potentially harmful effects upon healthy individuals who may come into contact with them.

Method used

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  • Near-infrared second window emitted micro-molecular rear earth complex fluorescence probe and preparation method thereof
  • Near-infrared second window emitted micro-molecular rear earth complex fluorescence probe and preparation method thereof
  • Near-infrared second window emitted micro-molecular rear earth complex fluorescence probe and preparation method thereof

Examples

Experimental program
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Effect test

Embodiment 1

[0038] Preparation of fluorescent probe molecule Nd-DOTA of small molecule rare earth complexes. Specific steps are as follows:

[0039] Weigh 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) into a single-necked round bottom flask, and dissolve with 1-3ml of water. Then weigh the NdCl 3 ·6H 2 O, dissolved in 1~2ml of water, NdCl 3 The aqueous solution was slowly added dropwise into the DOTA aqueous solution, and stirred at room temperature. Adjust the pH with NaOH solution to make it between 6.0 and 6.5. After reacting for 12 to 24 hours, stop the reaction. Anhydrous ether was slowly added for precipitation. Stand still and filter with suction to obtain a light purple solid powder. The fluorescent probe molecule Nd-DOTA, a small molecule rare earth complex, has strong absorption at 740nm and 802nm in aqueous solution, and is further excited with a laser at 808nm, and can observe the fluorescence emission peaks of rare earth neodymium ions at 1060nm and 1...

Embodiment 2

[0041] Preparation of fluorescent probe molecule Nd-DOTA-NHS of small molecule rare earth complexes. Specific steps are as follows:

[0042] Weigh the DOTA derivative DOTA-NHS ester (DOTA-NHS) into a single-necked round bottom flask, and dissolve it with 1-3ml of water. Then weigh the NdCl 3 ·6H 2 O, dissolved in 1~2ml of water, NdCl 3 The aqueous solution was slowly added dropwise to the DOTA-NHS aqueous solution, and stirred at room temperature. Adjust the pH with NaOH solution to make it between 6.0 and 6.5. After reacting for 12 to 24 hours, stop the reaction. Anhydrous ether was slowly added for precipitation. Stand still and filter with suction to obtain a white solid. The aqueous solution of the fluorescent probe molecule Nd-DOTA-NHS of the small molecule rare earth complex is excited by an 808nm laser, and the strong emission peak of the rare earth neodymium ion at 1060nm and the weaker fluorescence emission peak at 1330nm can be observed (see Figure 4 ).

Embodiment 3

[0044] Preparation of fluorescent probe molecule Nd-DOTA-FA of small molecule rare earth complex. Specific steps are as follows:

[0045] Weigh the solid of Nd-DOTA-NHS into a single-necked round bottom flask, add N,N-diisopropylethylamine (DIPEA) and N,N-dimethylformamide (DMF) (1 / 9), at room temperature Stir, then weigh amino PEG folic acid (NH 2 -PEG-FA), dissolved in 1-2ml of water, slowly added dropwise to the solution of Nd-DOTA-NHS, stirred at room temperature for 12-24 hours, then stopped the reaction, concentrated the reaction solution, washed several times with anhydrous ether, A yellow solid was obtained. The aqueous solution of the fluorescent probe molecule Nd-DOTA-FA of the small molecule rare earth complex is excited by an 808nm laser, and the strong emission peak of the rare earth neodymium ion at 1060nm and the weaker fluorescence emission peak at 1330nm can be observed (see Figure 5 ).

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Abstract

The invention belongs to the technical field of biological materials and particularly relates to a near-infrared second window emitted micro-molecular rear earth complex fluorescence probe and a preparation method thereof. The near-infrared second window emitted micro-molecular rear earth complex fluorescence probe comprises a complex coordinated by DOTA (1, 4, 7, 10-tetraazacyclododecan-1, 4, 7,10-tetraacetic acid) and rear earth Ln(III) metal, a complex coordinated by DOTA-NHS (DOTA-n-hydroxysuccinimide) ester and rear earth Ln(III) metal, and a reaction product of Ln-DOTA-NHS and amino-PEG(polyethylene glycol)-folic acid. By changing the functional groups in macrocyclic polyamine structures without affecting the coordinating ability of macrocyclic polyamines and rear earth ions, the near-infrared second window emitted micro-molecular rear earth complex fluorescence probe achieves tumor targeting effects after being specifically combined with tumor surface receptors and meanwhile achieves surgical excision of under the guidance of a near-infrared window. According to the variety of receptors to be modified by the micro-molecular rear earth complex fluorescence probe, the micro-molecular rear earth complex fluorescence probe can specifically target various tumors to achieve antibody-antigen immunoreaction, and through pairing of base pairs of DNA (deoxyribonucleic acid) sequences, to achieve gene expression.

Description

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Claims

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Application Information

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Owner FUDAN UNIV
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