MMP9-responsive T1/T2 switching type MR nano probe as well as preparation method and application thereof

A technology of MMP9 and nanoprobe, which is applied in the field of nanomaterials and molecular imaging, can solve the problems of MMP9 semi-quantitative analysis, low sensitivity, poor specificity and stability, etc., and achieve tumor-specific drug delivery and photothermal The effect of synergistic therapeutic effect, reduced interference, and simple preparation method

Active Publication Date: 2022-01-04
SHANGHAI FIRST PEOPLES HOSPITAL
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0006] The invention discloses a MMP9-responsive T1 / T2 switching MR nanoprobe and its preparation method and application. The nanoprobe can specifically switch from T2 contrast signal to T1 contrast signal at the tumor site, and can visualize the tumor In order to solve the problem of low sensitivity, poor specificity and stability of MR nanoprobes in the prior art and the inability to realize the semi-quantitative analysis of MMP9 in the tumor microenvironment

Method used

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  • MMP9-responsive T1/T2 switching type MR nano probe as well as preparation method and application thereof
  • MMP9-responsive T1/T2 switching type MR nano probe as well as preparation method and application thereof
  • MMP9-responsive T1/T2 switching type MR nano probe as well as preparation method and application thereof

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preparation example Construction

[0044] The preparation method of the T1 / T2 switching type MR nanoprobe of MMP9 response provided by the present invention comprises the following steps:

[0045] A method for preparing a T1 / T2 switching MR nanoprobe of MMP9 response, comprising the following steps:

[0046] S1, with PEG2000-NH 2 , MMP9 sensitive polypeptide Fmoc-GPLGL as raw material, adding a condensing agent to react, the reaction liquid is washed and dried by precipitation method, stirred and reacted in piperidine / DMF mixed solution, and separated to obtain PEG-MMP;

[0047] S2, using the PEG-MMP and the photosensitizer PIX as raw materials, adding a condensing agent to react, and separating to obtain an amphiphilic polymer (PEG-MMP) 2 -PIX;

[0048] S3, add ferric oleate, oleic acid and oleyl alcohol to the solvent, heat up to 100°C, remove residual water under negative pressure, and perform high-temperature reaction under argon; the reaction solution is cooled to room temperature, washed by precipitatio...

Embodiment 1

[0061] The preparation of embodiment 1, PMPSD nanoprobe

[0062] (1) Preparation of PEG-MMP

[0063] Take 1g PEG2000-NH 2 , 678mg Fmoc-GPLGL, 135mg 6-chloro 1-hydroxybenzotriazole (6-Chloro-1-hydroxibenzotriazol, Cl-HOBT) were dissolved in 1mL DMF solvent, and 124μL diisopropylcarbodiimide ( diisopropylcarbodiimide, DIC), and stirred at room temperature for 24 hours. After the reaction, the reactant was precipitated with ether, centrifuged, redissolved in DMF, and precipitated with ether. Repeated 3 times, and then vacuum-dried at 40°C for 24 hours. The product was then taken out and added to 5 mL of piperidine / DMF solution and stirred for two hours to remove Fmoc, and finally precipitated with ether three times to obtain the product PEG-MMP.

[0064] (2) Amphiphilic polymer (PEG-MMP) 2 -Preparation of PIX

[0065] Dissolve 532mg PEG-MMP, 141mg PIX, and 72mg Cl-HOBT in 1mL DMF solvent, add 66μLDIC dropwise, stir and react at room temperature for 24h, and wash the reaction ...

Embodiment 2

[0073] In vitro MMP9 response analysis of embodiment 2, PMPSD nanoprobe

[0074] Taking the T1 / T2 switching MR nanoprobe prepared in Example 1 as an example, the MMP9 response of the T1 / T2 switching MR nanoprobe of the present invention was analyzed.

[0075]Mix the T1 / T2 switching MR nanoprobe prepared in Example 1, MMP9 solution and SDS solution to prepare samples with equal nanoprobe concentrations but MMP9 concentrations of 0, 5, 10, 15 and 20 μg / mL, using 3.0 T's magnetic resonance scanner was tested, MR parameters: T2WI: TR = 2500ms, TE = 60ms, T1WI: TR = 522ms, TE = 12ms; T2-map images: TR = 1000ms, TE = 12-180ms; T1-map images: TR=4.0ms, TE2.0 ms; layer thickness=2mm, layer distance=1mm, FOV=13×13cm, matrix=324×339. T1weighted imaging T1WI and T2 weighted imaging T2WI under different MMP9 concentrations were tested. Repeat the scan three times and measure the relaxation time to calculate R1.

[0076] The result is as image 3 As shown, the T1 / T2 switching MR nanopr...

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Abstract

The invention discloses an MMP9 responsive T1 / T2 switching type MR nano probe as well as a preparation method and application thereof, and the MMP9 responsive T1 / T2 switching type MR nano probe is prepared by encapsulating USPIO and a hydrophobic drug in an amphiphilic polymer (PEG-MMP) 2-PIX through a self-assembly mode. The probe can specifically switch a T2 radiography signal to a T1 radiography signal under a tumor microenvironment MMP9 condition, and interference of background signals is reduced, so that the probe has high-sensitivity and specific imaging contrast performance, and high-quality imaging of a tumor part is realized; meanwhile, the probe can visualize the activity of the MMP9 in the tumor, and semi-quantitative analysis is carried out on the MMP9 through MR signals, so that the purpose of assisting in predicting disease prognosis and outcome can be achieved; and besides, by combining a fluorescence sensitizer PIX and an encapsulated hydrophobic drug, the probe disclosed by the invention can realize dual-mode imaging of transformation from a T2 contrast agent to a T1 contrast agent, and also realizes the effects of tumor specific drug delivery and photo-thermal synergistic therapy.

Description

technical field [0001] The invention belongs to the technical field of nanomaterials and molecular imaging, and in particular relates to a T1 / T2 switching MR nanoprobe responding to MMP9 and its preparation method and application. Background technique [0002] With the development of science and technology, magnetic resonance imaging (MRI) has become an effective means of clinical detection of diseases. Magnetic resonance imaging is a non-invasive imaging technique with high spatio-temporal resolution, which has broad application prospects in clinical medicine. [0003] In recent years, the development of MRI contrast agents has greatly promoted the application of MRI in the field of tumor diagnosis. In the tumor microenvironment, enzymes, pH, redox state, etc. are different from normal tissues. Using these biological information, people have designed many responses A single-mode MRI contrast agent can improve its selectivity for tumor tissue and further improve the accurac...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K49/12A61K49/14A61K49/18A61K45/06A61K41/00A61K31/704A61K31/337A61K31/69A61K38/05A61P35/00
CPCA61K49/126A61K49/14A61K49/186A61K49/1866A61K45/06A61K41/0052A61K31/704A61K31/337A61K31/69A61K38/05A61P35/00A61K2300/00Y02P20/55
Inventor 王中领陈安曹蓉朱仪
Owner SHANGHAI FIRST PEOPLES HOSPITAL
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