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Bimodal nanoprobes for image-guided brain tumor resection

A nano-probe, dual-mode technology, applied in the field of dual-mode nano-probes, can solve the problems of difficulty in precise excision, high mortality, and less superposition of surface electromagnetic fields, and achieves good signal enhancement performance and chemical stability. , Raman signal enhancement effect

Active Publication Date: 2018-03-27
FUDAN UNIV
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0002] According to literature reports, brain tumors have the characteristics of high incidence, recurrence rate, high mortality rate and low cure rate.
Among them, glioma accounts for 69% of all intracranial tumors, and is the deadliest type of brain tumor. The 5-year survival rate is less than 5%. Currently, the treatment of glioma is a recognized problem in the world. However, due to the characteristics of diffuse infiltrating growth of glioma, it is difficult to precisely locate it, making it very difficult to accurately remove it from the surrounding normal brain tissue during surgery.
However, currently commonly used gold nanoparticles such as gold nanospheres, gold nanorods, and gold nanostars have less surface electromagnetic field superposition and uneven distribution, resulting in only 0.1% of Raman molecular signals being enhanced to 10 8 times, while the overall signal enhancement efficiency is low

Method used

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  • Bimodal nanoprobes for image-guided brain tumor resection
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  • Bimodal nanoprobes for image-guided brain tumor resection

Examples

Experimental program
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Effect test

Embodiment 1

[0027] Example 1 Synthesis of dual-mode nanoprobes Au-AZ and Au-AK

[0028] according to figure 1In the synthetic route shown, polyethylene glycol Mal-PEG-CHO (6.0 mg, 3 μmol) and carbon-terminal lysine-modified Angiopep2 (7.2 mg, 3 μmol) were dissolved in 10 mL of DMF, and stirred at room temperature for 30 minutes to obtain compound 1. Methyl 3-mercaptopropionate (50mg, 0.42mmol) and hydrazine hydrate (60mg, 1.2mmol) were dissolved in 30mL ethanol, stirred at room temperature overnight, and the product was purified by silica gel column to obtain Compound 2; Compound 1 (13mg, 3.0μmol) Dissolve compound 2 (0.36 mg, 3.0 μmol) in 1.0M MES (pH 4.7) buffer solution and react overnight at room temperature, and the product is purified by a dialysis bag with a molecular weight cut-off of 1000 to obtain compound 3;

[0029] According to the above method, polyethylene glycol PEG-CHO (60mg, 0.03mmol) and compound 2 (3.6mg, 0.03mmol) were reacted to obtain compound 3a; diethylenetriamin...

Embodiment 2

[0031] The characterization of embodiment 2 bimodal nanoprobe Au-AZ and Au-AK

[0032] During the synthesis of dual-mode nanoprobes Au-AZ and Au-AK, an appropriate amount of the purified product was taken, dissolved in methanol, dropped on the potassium bromide window, dried with methanol, and the infrared spectrum was collected as shown figure 2 and image 3 As shown, 1720cm -1 The place is the stretching vibration peak of C=O in DTPA; 1044 and 1193cm -1 The place is the stretching vibration peak of S=O in IR783B; 2800-2960cm -1 The place is the stretching vibration peak of C-H in PEG; 1650 and 1550cm -1 is the infrared absorption peak of the amide bond in the targeting polypeptide Angiopep2. In the infrared spectrum of Au-AZ, 2100cm -1 Is the infrared absorption peak of N=N=N in the azide compound;

[0033] Take an appropriate amount of dual-mode nanoprobes, dissolve them in deionized water, drop them on the special copper grid for transmission electron microscopy, dr...

Embodiment 3

[0036] Example 3 Application of dual-modal nanoprobes in preoperative glioma localization

[0037] Establish a glioma xenograft nude mouse model according to the usual method;

[0038] The male nude mice were fixed on the brain stereotaxic instrument, and the prepared U87 cell suspension (10 μL / mouse) was injected into the striatum of the nude mice brain, and the tumor growth in the nude mice brain was observed by T2-MRI imaging after 2 weeks , T1-MRI imaging was used to investigate the size of glioma in the brain of nude mice and to conduct preliminary localization of the tumor. The mixture of nano-probes Au-AZ and Au-AK was injected into the tail vein. Performed on an MRI system (Biospect, Bruker), using head coil, isoflurane / oxygen mixed gas anesthesia, and warm water circulation system to maintain the body temperature of nude mice during scanning. The specific imaging parameters are as follows: FOV: 25×25mm, number of excitations: 2, Number of layers: 4 layers, layer thic...

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Abstract

The invention relates to bimodal nanoprobes and a preparation method thereof, and application of the bimodal nanoprobes to image-guided brain tumor resection, belonging to the field of molecular imaging probes. The nanoprobes use a gold nanoparticle as a carrier; the surface of the gold nanoparticle is modified by a magnetic resonance imaging group Gd<3+>-DTPA, a Raman reporter molecule IR783B, acyclooctyne group DBCO or an azido group N=N=N, polyethylene glycol, and an across-blood-brain-barrier targeting group Angiopep-2; and the targeting group Angiopep-2 specificity guides the nanoprobesacross blood-brain barriers through transcytosis, and the nanoprobes form aggregate in the acidic environment of brain tumors, so magnetic resonance signals and Raman scattering signals are enhanced at the same time. The bimodal nanoprobes employ a bimodal image technology of combined surface-enhanced resonant Raman scattering and magnetic resonance imaging, can locate tumors through magnetic resonance imaging before an operation, and utilize surface-enhanced resonant Raman scattering imaging to guide tumor resection during the operation. The bimodal nanoprobes provided by the invention have important scientific research and clinical significance to improvement of therapeutic effect on brain tumors and promotion of the clinical and translational practice of individual-based treatment methods.

Description

technical field [0001] The invention belongs to the field of molecular imaging, and relates to a molecular imaging probe, in particular to a dual-mode nanometer probe for image-guided brain tumor resection. The probe has the characteristics of crossing the blood-brain barrier, bimodal signal enhancement induced by a slightly acidic environment, and good stability. Background technique [0002] According to literature reports, brain tumors have the characteristics of high incidence, recurrence rate, high mortality rate and low cure rate. Among them, glioma accounts for 69% of all intracranial tumors, and is the deadliest type of brain tumor. The 5-year survival rate is less than 5%. Currently, the treatment of glioma is a recognized problem in the world. However, due to the characteristics of diffuse infiltrating growth of glioma, it is difficult to precisely locate it, making it very difficult to accurately remove it from the surrounding normal brain tissue during surgery. ...

Claims

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Application Information

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IPC IPC(8): A61K49/18A61K49/10A61K49/00
CPCA61K49/0021A61K49/0054A61K49/0056A61K49/0065A61K49/105A61K49/186A61K49/1866
Inventor 李聪高西辉岳琪
Owner FUDAN UNIV
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