Hypoxic imaging agent and preparation method and application thereof

An imaging agent and reaction technology, applied in the field of nano-imaging agents, can solve the problems of short blood half-life, cumbersome staining methods, and limited enrichment ability.

Active Publication Date: 2020-10-30
THE NAT CENT FOR NANOSCI & TECH NCNST OF CHINA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, nitroimidazole and its derivatives are mostly small molecules, which are easy to be metabolized, have a short blood half-life, and have limited enrichment...

Method used

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  • Hypoxic imaging agent and preparation method and application thereof
  • Hypoxic imaging agent and preparation method and application thereof
  • Hypoxic imaging agent and preparation method and application thereof

Examples

Experimental program
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Effect test

Embodiment 1

[0068] In this example, the following steps are used to prepare a multimodal imaging agent for tumor hypoxia:

[0069] (1) Disperse polyacrylic acid-modified iron oxide nanoparticles (UIO, 1.6mg Fe) in MES buffer (4mL) with a pH of about 6, and add EDC / NHS (15.2mg / 9.2mg);

[0070] (2) After reacting at room temperature for 2 hours, perform ultrafiltration purification with an ultrafiltration tube with a molecular weight cut-off of 10K, centrifuge at 6000 rpm for 20 minutes, then use deionized water to disperse the upper layer concentrate, and centrifuge again for washing three times;

[0071] (3) Disperse the activated UIOs in PBS buffer with pH 7.4, add L-cysteine ​​(4.84 mg, 40 μmol) and PLN (0.57 mg, 1 μmol), and react at room temperature for 8 hours;

[0072] (4) ultrafiltration method is the same as step (2), collect filtrate and measure 480nm place absorption and determine grafting rate by ultraviolet-visible spectrophotometer, ultrafiltration tube upper strata concentra...

Embodiment 2

[0077] In this example, the following steps are used to prepare a multimodal imaging agent for tumor hypoxia:

[0078] (1) Disperse polyacrylic acid-modified iron oxide nanoparticles (UIO, 0.8mg Fe) in MES buffer (4mL) with a pH of about 6, and add EDC / NHS (7.6mg / 4.6mg);

[0079] (2) After reacting at room temperature for 2 hours, perform ultrafiltration purification with an ultrafiltration tube with a molecular weight cut-off of 10K, centrifuge at 6000 rpm for 20 minutes, then use deionized water to disperse the upper layer concentrate, and centrifuge again for washing three times;

[0080] (3) Disperse the activated UIOs in PBS buffer at pH 7.4, add L-cysteine ​​(4.84 mg, 40 μmol) and PLN (0.29 mg, 0.5 μmol), and react overnight at room temperature;

[0081] (4) ultrafiltration method is the same as step (2), collect filtrate and measure 480nm place absorption and determine grafting rate by ultraviolet-visible spectrophotometer, ultrafiltration tube upper strata concentrated...

Embodiment 3

[0084] In this example, the following steps are used to prepare a multimodal imaging agent for tumor hypoxia:

[0085] (1) Disperse polyacrylic acid-modified iron oxide nanoparticles (UIO, 1.6mg Fe) in MES buffer (4mL) with a pH of about 6, and add EDC / NHS (15.2mg / 9.2mg);

[0086] (2) After reacting at room temperature for 2 hours, perform ultrafiltration purification with an ultrafiltration tube with a molecular weight cut-off of 10K, centrifuge at 6000 rpm for 20 minutes, then use deionized water to disperse the upper layer concentrate, and centrifuge again for washing three times;

[0087] (3) Disperse the activated UIOs in PBS buffer at pH 7.4, add L-cysteine ​​(2.42 mg, 20 μmol) and PLN (0.57 mg, 1 μmol), and react overnight at room temperature;

[0088] (4) ultrafiltration method is the same as step (2), collect filtrate and measure 480nm place absorption and determine grafting rate by ultraviolet-visible spectrophotometer, ultrafiltration tube upper strata concentrated ...

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Abstract

The invention provides a hypoxic imaging agent and a preparation method and application thereof. The hypoxic imaging agent is prepared from UIO-Pimo nanoparticles and a photoinitiator, the UIO-Pimo nanoparticle comprises a polyacrylic acid coated ferroferric oxide nanoparticle, a probe molecule which is connected to a polyacrylic acid fragment through an amido bond and is shown as a formula I, anda sulfydryl-containing molecule which is connected to the polyacrylic acid fragment through an amido bond. In a normal oxygen environment, the imaging agent provided by the invention is relatively small, uniform and stable in particle size, in a hypoxic environment, under the condition that reductase and NADPH coexist, the ultra-small particles can be assembled into an aggregate with a large size, fluorescence and nuclear magnetic resonance T2 imaging signals of the position where the ultra-small particles are located are enhanced, and therefore the sensitivity of hypoxic tumor detection is improved. In addition, the imaging agent has good penetrability, no obvious cytotoxicity and good biocompatibility. The preparation method is simple, mild in condition and low in cost.

Description

technical field [0001] The invention belongs to the technical field of nano-imaging agents, and relates to an anoxic imaging agent and its preparation method and application. Background technique [0002] Hypoxia is a common phenomenon in most solid tumors and is closely related to tumor occurrence, development, metastasis and drug resistance (J.Natl.Cancer I.2007,99(19),1441-1454.). The 2019 Nobel Prize in Physiology and Medicine was awarded to the discoverer of its related factor (HIF-1α). Therefore, how to realize the imaging of hypoxic cells is very important for tumor diagnosis. However, it is very limited to determine the lesion site or lesion degree by a single mode of imaging, and it will become a future development trend to be able to image the hypoxic area of ​​the tumor in multiple ways. [0003] The sensitivity of fluorescence imaging is particularly high, but the tissue penetration ability is relatively poor; the penetrating power of nuclear magnetic imaging i...

Claims

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Application Information

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IPC IPC(8): A61K49/00A61K49/18A61K49/12
CPCA61K49/0002A61K49/0021A61K49/0093A61K49/1854A61K49/126
Inventor 陈春英周会鸽李佳阳郭梦雨
Owner THE NAT CENT FOR NANOSCI & TECH NCNST OF CHINA
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