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A fa-cus/ce6-gd nano-diagnosis and treatment probe of conjugated gadolinium and its preparation method and application

A ce6-gd, nanotechnology, applied in the preparations for in vivo experiments, general/multifunctional contrast agents, medical preparations with inactive ingredients, etc. The rate and penetration depth are low, not enough to kill tumor cells, etc., to achieve the effect of good dispersion and biocompatibility, and wide application prospects.

Active Publication Date: 2021-10-29
NANJING UNIV OF POSTS & TELECOMM
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0003] However, the uneven heat distribution of PTT makes it insufficient to kill all tumor cells, and excessive local temperature can easily cause heat shock
In addition, due to the hypoxia of cancer cells and the gradual consumption of intracellular oxygen, the effect of oxygen-dependent PDT treatment will gradually decrease. Therefore, monotherapy (such as PTT, PDT) can no longer meet the requirements of modern medicine for eradicating cancer cells and low side effects
[0004] At present, in the field of cancer diagnosis, several auxiliary imaging techniques that have been applied to guide phototherapy have certain limitations, such as positron emission tomography (PET) has the disadvantage of short half-life of radionuclides, computed tomography (CT) Low spatial resolution, easy to cause toxic side effects (such as iodine allergy), low spatial resolution and penetration depth of fluorescence imaging (FL)

Method used

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  • A fa-cus/ce6-gd nano-diagnosis and treatment probe of conjugated gadolinium and its preparation method and application
  • A fa-cus/ce6-gd nano-diagnosis and treatment probe of conjugated gadolinium and its preparation method and application
  • A fa-cus/ce6-gd nano-diagnosis and treatment probe of conjugated gadolinium and its preparation method and application

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preparation example Construction

[0042] A kind of preparation method of the FA-CuS / Ce6-Gd nanometer diagnosis and treatment probe of conjugated gadolinium, the method comprises the following steps:

[0043] S1: Synthesis of amino-modified CuS nanoparticles;

[0044] in CuCl 2 2H 2 In the aqueous solution of O, add a certain mass of HS-PEG-NH 2 , adjust the pH of the solution to 9.0-10.0 through NaOH solution, and then add thioacetamide (CH 3 CSNH 2 ) into the mixed solution, heated the mixture to 50-70°C, reacted for 2-4 hours, left to cool, washed by ultrafiltration, and washed three times with phosphate buffered saline solution to obtain amino-modified water-soluble CuS nanoparticles, HS -PEG-NH 2 The molecular weight is 2000;

[0045] S2: Preparation of Ce6-modified CuS nanoparticles;

[0046] Dissolve Ce6 in DMSO at a concentration of 1 mg / mL, add 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC) and N-hydroxysuccinyl Amine (NHS) was stirred at room temperature for 2-4 hours; the a...

Embodiment 1

[0052] Formation of amino-modified CuS template: 9 mg CuCl 2 2H 2 O was dissolved in 12mL ultrapure water, and 21mgHS-PEG-NH 2 , add 1M NaOH solution dropwise, adjust the pH of the solution to 9.0, then add 8mg thioacetamide to the mixed solution, heat the mixture to 50°C, react for 2h, ultrafilter, wash with PBS (molecular weight cut off 10KDa, 5000rpm ) three times to get H 2 N-PEG-CuS NPs. figure 2 and Figure 4 respectively H 2 The transmission electron microscope image of N-PEG-CuS NPs and the size distribution image under dynamic light scattering, it can be seen that the H 2 The particle diameter of N-PEG-CuS NPs is about 30 nm. Figure 4 In , the ordinate is the number of nanoparticles, and the abscissa is the size of the particle diameter.

Embodiment 2

[0054] S1: Refer to Example 1 for the formation of amino-modified CuS templates.

[0055] S2: Ce6 activation: 6.3 mg of chlorin e6 was dissolved in dimethylsulfoxide at a concentration of 1 mg / mL, and 40.3 mg of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide was added Hydrochloride (EDC) and 24.2mg of N-hydroxysuccinimide (NHS) were stirred at room temperature for 2h.

[0056] S3: Ce6 modified CuS nanoparticles: Add the activated chlorin e6 solution to the CuS solution, stir overnight in the dark, wash with ultrafiltration water to remove the organic solvent dimethyl sulfoxide and unreacted Ce6, and collect CuS / Ce6 nanoparticles.

[0057] S4: Folic acid modification of CuS nanoparticles: Add 21 mg of HS-PEG-FA aqueous solution to the aqueous solution of CuS-Ce6 nanoparticles obtained in step S3, mix and stir for 6 hours, wash with ultrafiltration water three times, and couple folic acid to CuS through sulfhydryl groups the surface of the nanoparticles.

[0058] S5: Gd 3+ C...

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Abstract

The invention discloses a FA-CuS / Ce6-Gd nano-diagnosis and treatment probe of conjugated gadolinium and its preparation method and application, using amino-modified CuS nanoparticles as a template, and gradually modifying the photosensitizer chlorin, Folic acid with tumor targeting function is finally prepared by chelating gadolinium ions. The present invention combines CuS nanoparticles with significant photothermal effects in the near-infrared region with chlorin with excellent photosensitizing effects through surface modification, and at the same time modifies the surface of the targeted therapeutic agent folic acid and coordination chelation for MRI. Paramagnetic gadolinium ions are finally made into water-soluble nano-therapeutic probes for multimodal imaging-guided photothermal / photodynamic synergistic therapy. The nanoprobe solves the problems of insufficient drug targeting and poor treatment effect of monotherapy. At the same time, it introduces advanced imaging technology to realize the precise diagnosis of cancer. It has the advantages of low toxicity, water solubility, dispersibility and good biocompatibility. .

Description

technical field [0001] The invention relates to a FA-CuS / Ce6-Gd nanometer diagnosis and treatment probe of conjugated gadolinium, a preparation method and application thereof, which can be used in the technical field of biomedicine. Background technique [0002] In recent years, in the field of tumor treatment, new phototherapy (including photothermal and photodynamic therapy) is gradually replacing traditional surgery, chemotherapy and radiotherapy. Among them, near-infrared light (NIR) has been used as an effective light source for inducing phototherapy due to its noninvasiveness, deep tissue penetration, and nontoxic side effects. Photothermal therapy is a treatment method that uses materials with high photothermal conversion efficiency to convert light energy into heat energy to kill tumor cells. Photodynamic therapy (PDT) is another treatment modality of light therapy, under external laser irradiation, the photosensitizer (PS) enriched in the tumor area absorbs light e...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K49/00A61K41/00A61K47/52A61K47/54A61K49/22A61K49/08A61P35/00
CPCA61K41/0052A61K41/0071A61K49/0002A61K49/085A61K49/221A61K47/52A61K47/545A61P35/00A61K2300/00
Inventor 沈清明戴叶能王兵孙志权范曲立
Owner NANJING UNIV OF POSTS & TELECOMM
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