A multimodal nanoprobe for guiding precise resection of glioma

A nano-probe and multi-modal technology, applied in preparations for in vivo experiments, general/multifunctional contrast agents, drug delivery, etc., to achieve weak autofluorescence, high sensitivity, and simple operation

Active Publication Date: 2022-05-17
AFFILIATED HUSN HOSPITAL OF FUDAN UNIV +1
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  • 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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  • A multimodal nanoprobe for guiding precise resection of glioma
  • A multimodal nanoprobe for guiding precise resection of glioma
  • A multimodal nanoprobe for guiding precise resection of glioma

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 shows The results show that the particle size of the nanoprobe 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] Figure 3 shows It is shown that the average diameter of AuP-FAL is 61.2nm and 60.7nm, and the average zeta potential is -23.3mV.

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Abstract

The invention belongs to the field of molecular imaging probes, and relates to a multimodal nanoprobe for guiding the precise resection of glioma, in particular to a magnetic resonance / Raman nano-gold particle probe capable of targeting EGFRvIII-positive glioma Synthesis of its intermediates, and its application in preoperative precise planning and intraoperative real-time navigation resection of glioma. The nanoprobe is based on spherical gold nanoparticles (AuNS), and the paramagnetic chelating agent Gd is connected on its surface. 3+ ‑DTPA and Raman signaling molecule IR783B, and PEG as a carrier to link the polypeptide FALGEA targeting EGFRvIII. The nanoprobe helps to ensure the consistency of preoperative planning and intraoperative resection, and can overcome the shortcomings of existing imaging probes such as short circulation time, non-targeting, and difficulty in penetrating the complete blood-brain barrier. High signal-to-noise ratio tracking and precise resection of gliomas, especially EGFRvIII-positive gliomas.

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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Patent Type & AuthorityPatents(China)
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