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Fluorescent multi-mode molecular imaging and drug-loaded breast cancer diagnosis and treatment integrated nanoprobe and preparation method and application thereof

A molecular imaging and nanoprobe technology, applied in the field of medical diagnosis, can solve the problems of inability to obtain the diagnosis results at the same time and carry out symptomatic treatment, the increase of pan-host properties, and the high lipid solubility of drugs, so as to improve bioavailability and treatment. effect of effect

Pending Publication Date: 2020-12-25
NANJING NORMAL UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] However, the conventional route of administration of SC13 or its derivatives is oral administration. The limitation is that the drug is highly fat-soluble, its molecules bind to multiple targets, and the pan-host property increases, resulting in enhanced toxicity of the drug. , with poor solubility and metabolic clearance
And the local release rate of the drug is low, so that the therapeutic effect on the tumor cannot be maximized
In addition, simple administration of SC13 or its derivatives cannot achieve the effect of simultaneously obtaining diagnostic results and carrying out symptomatic treatment

Method used

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  • Fluorescent multi-mode molecular imaging and drug-loaded breast cancer diagnosis and treatment integrated nanoprobe and preparation method and application thereof
  • Fluorescent multi-mode molecular imaging and drug-loaded breast cancer diagnosis and treatment integrated nanoprobe and preparation method and application thereof
  • Fluorescent multi-mode molecular imaging and drug-loaded breast cancer diagnosis and treatment integrated nanoprobe and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0075] Example 1 Preparation method of 119F-MR / fluorescence multimodal molecular imaging and drug-loaded integrated nanoprobe for diagnosis and treatment of breast cancer

[0076] I, will target the small molecule inhibitor SC13 of FEN1 (such as figure 1 shown) is uniformly mixed with surfactants and fluorescent dyes, and the surfactants physically coat the small-molecule inhibitor SC13 targeting FEN1 due to surface tension (such as figure 1shown). Then it was dissolved in a volatile organic solvent, stirred at room temperature for 10 minutes, and the organic solvent was evaporated to dryness by a rotary evaporator, then dried in a vacuum oven at 37°C for 12 hours, and finally dispersed in water by ultrasonic treatment to obtain a mixture, spare.

[0077] II. Uniformly disperse perfluorocarbons in the mixture obtained in step I, add glycerin and water drop by drop, and mix in a high-pressure homogenizer for 5 minutes to prepare 19F-MR / fluorescent multi-mode molecular imaging...

Embodiment 2

[0091] Example 2 The use of 19F-MR / fluorescence multimodal molecular imaging and drug-loaded integrated nanoprobe for diagnosis and treatment of breast cancer (prepared in Example 1) as an imaging contrast agent.

[0092] 1. 19F-MRI phantom test of this probe The nanoprobe solution prepared in Example 1 was blended with 1.7% Agrose sol, and the final concentrations were prepared to be 8.79mmol / L, 17.55mmol / L, and 35.13mmol / L respectively , 70.48mmol / L, 140.87 mmol / L phantom sample, test its 19F imaging ability, the results are as follows Figure 4 As shown, it can be seen from the results that the 19F signal enhancement ability of the probe is positively correlated with the sample concentration, and the signal increases linearly with the increase of the sample concentration.

[0093] 2. Magnetic resonance imaging after intravenous delivery of the probe First, the nude mice were anesthetized with isoflurane gas. After the anesthesia was successful, 3 nude mice were sequentially...

Embodiment 3

[0095] Example 3 The curative effect evaluation of the probe (prepared in Example 1) targeted therapy.

[0096] 1. Evaluation of the efficacy of the probe (prepared in Example 1) at the cellular level.

[0097] The cells were made into a single cell suspension with a culture solution containing 10% fetal bovine serum, and 20,000 cells per well were seeded into a 96-well plate with a volume of 200 ul per well. After overnight incubation, different concentrations of nanoprobes were added. After 24 hours, MTT solution and dimethyl sulfoxide were added, and shaken on a shaker at low speed for 15 minutes. The absorbance of each well was measured at OD570nm using a microplate reader.

[0098] Depend on Figure 6 It can be seen that after incubation with PFCE, all the cell viability was greater than 90%, which indicated that PFCE did not cause significant cytotoxicity to the MDA-MB-231 cell line. PFCE-SC13 had a higher level of cytotoxicity than PFCE and saline at 24 hours. The ...

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Abstract

The invention provides an FEN1-targeted 19F-MR / fluorescence multi-mode molecular imaging and drug-loaded breast cancer diagnosis and treatment integrated nanoprobe and a preparation method and application thereof. The probe is nanoparticles formed by coating a perfluorinated carbon carrier with a mixture of a surfactant containing a FEN1-targeted small molecule inhibitor SC13 or a derivative thereof and a fluorescent dye; and a mixed solution is uniformly dispersed in water and glycerin, ultrasonic treatment is performed to remove uncoated components, and purifying is performed to obtain the drug-loaded nanoparticles for 19F-MR imaging. The probe can realize in-vivo 19F-MR molecular imaging and optical imaging, and realize molecular level accurate diagnosis of solid tumors such as breast cancer; not only can the effect of targeted combination diagnosis of the solid tumors be achieved, but also targeted treatment can be achieved; and by means of the characteristic that perfluoro in thenucleus can carry and release a large amount of oxygen, the hypoxic microenvironment in the tumors is improved, and the chemotherapy sensitization effect and diagnosis and treatment of the solid tumors are integrated.

Description

technical field [0001] The invention belongs to the technical field of medical diagnosis, and in particular relates to a preparation method and application of a 19F-MR / fluorescence multi-mode molecular imaging and drug-loaded integrated nanoprobe for tumor diagnosis and treatment for breast cancer diagnosis and treatment. Background technique [0002] So far, breast cancer is still the most common cancer in women, and its incidence rate continues to rise. Therefore, it is extremely urgent to develop new and effective drugs for the treatment of breast cancer. Studies have shown that FEN1 is overexpressed in breast cancer cells, and this patent uses the MCF7 breast cancer cell line as a research model, proving that FEN1 is essential for the proliferation and drug resistance of breast cancer cells. DNA fragment endonuclease 1 (FEN1) plays a key role in maintaining genome stability and integrity by participating in DNA replication and repair. FEN1 is a metallonuclease with stru...

Claims

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Application Information

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IPC IPC(8): A61K49/18A61K49/10A61K49/00A61K9/51A61K47/06A61K31/519A61P35/00
CPCA61K49/1824A61K49/10A61K49/0002A61K49/0021A61K9/5123A61K31/519A61P35/00
Inventor 郭志刚何凌峰朱红桥张苗苗
Owner NANJING NORMAL UNIVERSITY
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