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Rare earth optical probe and preparation method and application thereof

An optical probe and rare earth technology, which is applied in the field of rare earth optical probes and its preparation, can solve the problems of hindering the efficient enrichment of probes and low ligand binding efficiency, and achieve enhanced tumor enrichment rate and retention time, and good application The effect of foreground, enhanced resolution and signal-to-noise ratio

Active Publication Date: 2022-08-05
PEKING UNIV SHENZHEN HOSPITAL
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0006] In view of the above-mentioned deficiencies in the prior art, the purpose of the present invention is to provide a rare earth optical probe and its preparation method and application, aiming at solving the problem of acceptors on the surface of the rare earth optical probe and modifying the surface of the rare earth optical probe in the prior art. The ligand binding efficiency of the low-density lipoprotein is low, which hinders the high-efficiency enrichment of the probe in the tumor site.

Method used

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  • Rare earth optical probe and preparation method and application thereof
  • Rare earth optical probe and preparation method and application thereof
  • Rare earth optical probe and preparation method and application thereof

Examples

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Effect test

Embodiment 1

[0080] Preparation of Rare Earth Optical Probes with Three-layer Structure

[0081] First, NaYbF was prepared by co-precipitation 4 : 2% Er, 2% Ce kernel. 0.96mmol YbCl 3 ·6H 2 O, 0.02mmol ErCl 3 ·6H 2 O and 0.02mmol CeCl 3 ·7H 2 A mixture of O with 6 mL of oleic acid and 15 mL of octadecene was added to a 250 mL flask, and the solution was stirred and heated to 150°C for 60 minutes. Subsequently, after the solution was cooled to 40 °C, 2.5 mmol NaOH and 4.0 mmol NH were mixed 4 F was dissolved in 6ml and 8ml methanol, respectively, then the NaOH solution and NH 4 The F solution was added dropwise to the above rare earth salt precursor solution in turn. After keeping at room temperature for 30 minutes, the mixed solution was successively heated to 50 °C for 30 minutes, heated to 70 °C for 20 minutes, and finally held at 100 °C for 30 minutes to remove excess. methanol and water. Then the solution was rapidly heated to 300° C. and kept for 50 min, the heating was stop...

Embodiment 2

[0087] Evaluation of NIR-IIb Fluorescence Emission of Rare Earth Optical Probes

[0088] The rare-earth optical probes with different Yb doping concentrations are roughly the same as those in Example 1, except that when the second shell layer is coated by thermal cracking, the amount of trifluoroacetate raw material is changed, as follows: NaYF 4 :x%Yb 3+ (x=0%, 10%, 30%, 50%, 100%) shell. (1-x%) / 2mmol prepared Y(CF 3 COO) 3 , Yb(CF prepared by x% / 2mmol 3 COO) 3 , 1mmol CF 3 COONa and 0.25 mmol (2.5 mL) core nanocrystals (NaYbF 4 : 2% Er, 2% Ce NPs) was first added to the mixed solution of 10 mL of oleic acid and 10 mL of octadecene. The mixture was then heated to 120°C for 45 min and then to 300°C for 30 min. Subsequently, the reaction mixture was naturally cooled to room temperature, and the product was obtained by washing with ethanol and centrifugation.

[0089] The fluorescence emission intensity of NIR-IIb obtained by rare-earth optical probes with different Yb ...

Embodiment 3

[0092] Bioorthogonal NIR-IIb Rare Earth Optical Probe

[0093] First, in NaYbF 4 : 2%Er, 2%Ce@NaYbF 4 @NaYF 4 : 30% Nd surface modification DSPE-PEG-NH 2NPs, the specific steps are as follows: 35mg DSPE-PEG-NH 2 (in 2 ml of chloroform) was mixed with 10 mg of DCNPs (in 1 ml of chloroform), stirred at room temperature overnight, and then heated to 60°C to allow complete evaporation of the organic solvent. Then 2 mL of water was added to the above product, sonicated for 10 min, and the NPs@DSPE-PEG-NH was collected 2 , centrifuged at 10,000 rpm for 10 min, washed with water 3 times, and finally dispersed in 2 mL of distilled water.

[0094] Subsequently, DBCO-NHS was combined with NH on the surface of the optical probe through an amidation reaction. 2 connect. Specifically, 1.0 mg of DBCO-NHS was dissolved in a solution containing 200 μL of DMF and 50 μL of TEA, 1 mL of prepared DCNPs@NH2), stirred overnight at room temperature, centrifuged at 12,000 rpm for 15 min, washe...

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Abstract

The invention discloses a rare earth optical probe as well as a preparation method and application thereof. The rare earth optical probe comprises an inner core NaYbF4: Er < 3 + >, Ce < 3 + >, a shell layer NaYF4: Yb < 3 + >, a shell NaYF4: Nd < 3 + > and dibenzocyclooctyne modified on the surface of the shell NaYF4: Nd < 3 + >. The rare earth optical probe has a three-layer structure, capability loss caused by unnecessary cross relaxation between rare earth ions (Er < 3 + > ions and Nd < 3 + > ions) is avoided, and the rare earth optical probe has high-brightness NIR-IIb fluorescence emission; a functional group-alkynyl is modified on the surface of the probe, so that the probe is endowed with biological orthogonality; when the rare earth optical probe and tumor extracellular vesicles with homologous targeting are subjected to efficient biological orthogonal combination in a living body, the tumor enrichment rate and residence time of the optical probe can be increased, and long-time dynamic fluorescence imaging of living tumor can be realized.

Description

technical field [0001] The invention relates to the technical field of optical biological imaging, in particular to a rare earth optical probe and a preparation method and application thereof. Background technique [0002] Rare earth-doped nanoparticles (NPs) have excellent optical properties, such as no photobleaching, no scintillation, narrow emission bandwidth, and long lifetime, making them a promising class of optical probes. More importantly, the doping of erbium ions (Er 3+ ) down-converting nanocrystals (DCNPs) with characteristic fluorescence emission peaks at 1525 nm, suitable for in vivo imaging of NIR-IIb. [0003] Currently, Er 3+ Ion-doped optical probes have been designed and used to achieve micrometer-scale resolution for whole-body and cerebral vascular imaging at millimeter depths. Although rare earth optical probes have made some progress in the field of in vivo fluorescence imaging, only using the traditional enhanced permeability and retention (EPR) e...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C09K11/85C09K11/02B82Y30/00A61K49/00
CPCC09K11/7773C09K11/02C09K11/025A61K49/0019A61K49/0052A61K49/0054A61K49/0093B82Y30/00
Inventor 穆婧李慧钟艳凤王淑敏
Owner PEKING UNIV SHENZHEN HOSPITAL
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