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Ultrasonic image nanoprobe as well as preparation method and application thereof

A nano-probe and ultrasound imaging technology, applied in the field of nano-biomedicine, can solve the problems that microbubble contrast agents cannot efficiently penetrate tumor blood vessels, cannot achieve accurate diagnosis of tumor acidic microenvironment, and hinder accurate diagnosis of tumor acidic microenvironment, etc. Achieve the effects of cheap raw materials, strong anti-interference ability and few synthesis steps

Pending Publication Date: 2022-02-22
EAST CHINA NORMAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

When the microbubble contrast agent is used to detect the acidic microenvironment of the tumor, the microbubbles will diffuse, fuse or even rupture under the influence of the sound pressure and the pressure exerted by the external operator, resulting in unstable ultrasonic signals and the inability to achieve tumor acidity. Accurate diagnosis of microenvironment; 2. Size mismatch of microbubble contrast agent
As a commonly used clinical ultrasound contrast agent, microbubbles are at the micron level; however, the size of tumor microvessels is at the nanometer level, which makes the microbubble contrast agent unable to efficiently penetrate tumor blood vessels, which hinders its accurate diagnosis of the acidic microenvironment of the tumor

Method used

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  • Ultrasonic image nanoprobe as well as preparation method and application thereof
  • Ultrasonic image nanoprobe as well as preparation method and application thereof
  • Ultrasonic image nanoprobe as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0051] Example 1: Ultrasound imaging nanoprobe BiF 3 Preparation and Characterization of @PDA@PEG

[0052] (1) 2mmol bismuth nitrate pentahydrate (Bi(NO 3 ) 3 ·5H 2 O) and 48mmol ammonium fluoride (NH 4 F) Disperse in 20mL and 40mL of ethylene glycol respectively, stir the two solutions at 30°C until they are clear and transparent, then mix them together and react for 4 hours. 3 Disperse and store in 20mL ethanol.

[0053] (2) Take 10mL of the BiF obtained in the above step (1) 3 Ethanol solution, centrifuged to discard the supernatant, the remaining BiF 3 Nanoparticles were dispersed in 200 mL of deionized water, 400 mg of dopamine hydrochloride (PDA) was added to the above system, and after stirring for 30 min, 500 μL of concentrated ammonia water (NH 3 ·H 2 O), continue stirring reaction 12h. After the reaction, centrifuged and washed 2-3 times with deionized water, the obtained BiF 3 @PDA is dispersed in 20mL deionized water.

[0054] (3) Take 10mL of BiF obtain...

Embodiment 2

[0058] Embodiment 2: Using the simulation calculation method of the coupling of sound field and cavitation deformation, the results of detecting the acidic environment under the interference of external pressure by the ultrasonic imaging nanoprobe and bubbles prepared in Embodiment 1 of the present invention are simulated.

[0059] The final result is attached image 3 As shown, it is known from the calculation results that the ultrasonic imaging nanoprobe self-agglomerates into larger particles in an acidic environment, and at the same time increases the local density, resulting in a significant increase in the acoustic impedance difference with the surrounding area, and then in a In the case of external pressure, the influence of the probe on the sound field is almost unchanged, indicating that the effect of the probe on the sound field propagation is only affected by the acidic environment; however, when the bubble detects the acidic environment, the external When pressure ...

Embodiment 3

[0060] Example 3: Ultrasound imaging nanoprobe BiF 3 @PDA@PEG In Vitro Ultrasound Signal Research

[0061] (1) BiF prepared in steps (2) and (3) in Example 1 of the present invention 3 @PDA (for simulating physiological environment in vivo, pre-experiment for nanoprobe detection acid environment) and BiF 3 @PDA@PEG is made into a 7000ppm solution with pure water.

[0062] (2) Preparation of Na with pH=5.0, 6.0, 6.5 2 HPO 4 2H 2 O-KH 2 PO 4 Buffer solution, using buffer solutions with different pH values ​​to prepare 7000ppm BiF 3 @PDA@PEG aqueous solution, ultrasonic imaging after standing for 1h, the results are shown in the attachment Figure 4 , it can be seen from the results that BiF 3 When the @PDA@PEG nanoprobe does not encounter acid, it is in a monodisperse state in water, with a small local density, and the acoustic impedance formed by the surrounding environment is not much different, and the ultrasonic signal generated by it is almost indistinguishable fro...

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Abstract

The invention discloses a preparation method of an ultrasonic imaging nano probe for detecting a tumor acidic microenvironment, and belongs to the field of nano biomedicine. The preparation method of the ultrasonic image nanoprobe, disclosed by the invention, is mild in reaction condition and simple in synthesis step. The ultrasonic imaging nanoprobe disclosed by the invention can be used for realizing accurate diagnosis of an acidic microenvironment of a tumor in a tumor-bearing mouse by utilizing a medical ultrasonic imaging technology, and has the advantages of strong anti-interference capability, good signal stability, good biocompatibility and the like.

Description

technical field [0001] The invention belongs to the field of nano-biomedicine, and relates to a preparation method of an ultrasonic imaging nano-probe for detecting the acidic microenvironment of tumors. Background technique [0002] Tumor acidic microenvironment, as a common feature of solid tumors, is closely related to tumor invasion, metastasis, immune evasion and multidrug resistance. The use of medical imaging methods to accurately detect the acidic microenvironment of tumors in real time is of great significance for improving the precise treatment of tumors. At present, a variety of imaging techniques, including MR and CT, have been used for real-time monitoring of the acidic microenvironment of tumors. For example, Ni et al. used NaGdF 4 @PLL nanoprobe, through the strategy of fusion of T1-MRI structural image and CEST functional image, realizes dual-mode MR image of tumor structure and acidic microenvironment. In addition, Meng et al. innovatively proposed the us...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K49/22B82Y40/00
CPCA61K49/225A61K49/221B82Y40/00
Inventor 益艳孟宪福步文博
Owner EAST CHINA NORMAL UNIV