Multi-mode nanoprobe for guiding accurate glioma excision

A nano-probe and multi-modal technology, which is applied in general/multifunctional contrast agents, preparations for in vivo experiments, nuclear magnetic resonance/magnetic resonance imaging contrast agents, etc., to achieve weak autofluorescence, high sensitivity, and simple operation Effect

Active Publication Date: 2018-11-02
AFFILIATED HUSN HOSPITAL OF FUDAN UNIV +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] At present, there is no report on the use of multimodal gold particle probes targeting EGFRvIII for glioma imaging and surgery. Based on the current state of the art, the inventors of this application intend to provide a method for Multimodal nanoprobes for guiding precise resection of glioma

Method used

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  • Multi-mode nanoprobe for guiding accurate glioma excision
  • Multi-mode nanoprobe for guiding accurate glioma excision
  • Multi-mode nanoprobe for guiding accurate glioma excision

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0030] Embodiment 1, the synthesis of targeted nanoprobe and control probe

[0031] Synthetic route such as figure 1 As indicated, polyethylene glycol SH-PEG-NHS (compound 1, 40mg, 0.02mmol) and polypeptide FAL (12.12mg, 0.02mmol) were dissolved in 0.3mL DMF, stirred at room temperature for 2h to obtain PEG derivative 2. 500mL 0.294mM tetrachloroauric acid solution, boiled, quickly added 5mL of 38.8mM sodium citrate aqueous solution, reflux reaction for 5min, the reaction product was purified by a dialysis bag with a molecular weight cut-off of 10000 to obtain citric acid-modified gold nanoparticles 3, particle size About 60nm. Diethylenetriaminepentaacetic dianhydride (10mg, 28μmol) and 2-mercaptoethylamine (1mg, 28μmol) were dissolved in 0.5mL DMF, stirred at room temperature for 4h to obtain compound 4. Compound 4 was added dropwise into 10 mL of gold nanoparticles 3 (0.13 μM), and reacted with stirring at room temperature overnight to obtain gold nanoparticles 5. GdCl ...

Embodiment 2

[0032] Embodiment 2, the transmission electron microscope picture of nanoprobe

[0033] Take an appropriate amount of nano-probes, drop them on the special copper grid for transmission electron microscopy, place them in a 40-degree oven for drying, and collect TEM images through transmission electron microscopy, as shown in figure 2 The results show that the particle size of the nano-probe is about 60nm, the dispersion is uniform, and the gold core is wrapped with a translucent polyethylene glycol layer.

Embodiment 3

[0034] Embodiment 3, to the mensuration of the hydrodynamic particle size distribution of nanoprobe and Zeta potential

[0035] Determination of the hydrodynamic radii of the target nanoprobe AuP-FAL and the reference probe AuP-PEG by dynamic light scattering at room temperature; equipment calibration was performed with a 2.0 mg / ml bovine serum albumin standard solution in distilled water , the sample was filtered with a 0.45μm filter head and diluted to 100g / mL with 1X PBS of pH 7.4, and the hydrodynamic radius and size distribution were calculated by a regularized formula; when the surface charge of the nanoprobe was determined, a Zeta Calibrate the equipment with a standard solution with a potential of -50mV, filter the nanoprobe drug solution with a 0.45μm filter head and dilute it to 200g / mL with 10mM NaCl solution;

[0036] image 3 It is shown that the average diameter of AuP-FAL is 61.2 nm and 60.7 nm, and the average zeta potential is -23.3 mV.

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Abstract

The invention belongs to the field of molecular image probes, relates to a multi-mode nanoprobe for guiding accurate glioma excision, and particularly relates to a magnetic resonance / raman gold nanoparticle probe with EGFRvIII positive glioma targeting effect and synthesis of an intermediate thereof, and application thereof in accurate preoperative glioma planning and real-time intraoperative excision navigation. The nanoprobe is characterized in that spherical golden nanoparticles (AuNs) is used as a substrate, and a paramagnetism chelating agent Gd<3+>-DTPA and a raman signal molecule IR783B are connected to the surface of the substrate; PEG is used as a supporter for connecting polypeptide FALGEA which targets the EGFRvIII. The nanprobe ensures the consistence of preoperative planningand intraoperative excision, and overcomes the shortages that an image probe in the prior art is short in cycling time, free from targeting performance, and hard to penetrate a complete blood brain barrier; and glioma, particular EGFRvIII positive glioma can be tracked with high signal-to-noise ratio and accurately excised.

Description

technical field [0001] The invention belongs to the field of molecular imaging probes, and relates to a multimodal nanoprobe, in particular to a multimodal nanoprobe for guiding precise resection of gliomas, and in particular to a magnetic nanoprobe capable of targeting EGFRvIII-positive gliomas. Synthesis of resonance / Raman gold nanoparticle probes and their intermediates, and their application in preoperative precise planning and intraoperative real-time navigational resection of glioma. Background technique [0002] The prior art discloses that among primary intracranial tumors, glioma has the highest incidence rate, close to 40.5%, and has the characteristics of short survival, high recurrence rate and high mortality rate; especially glioblastoma, although in recent years Comprehensive treatment (including surgery, radiotherapy, chemotherapy) has made great progress, but the median survival time is only 14.6 months. At present, surgery is still the first choice for most...

Claims

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Application Information

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IPC IPC(8): A61K49/00A61K49/14A61K49/12A61K49/08A61K49/18
CPCA61K49/0002A61K49/0013A61K49/08A61K49/126A61K49/14A61K49/186A61K49/1866
Inventor陈亮毛颖岳琪高西辉李聪
OwnerAFFILIATED HUSN HOSPITAL OF FUDAN UNIV