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CN-122005878-A - Probe system for detecting Ox-LDL and application thereof

CN122005878ACN 122005878 ACN122005878 ACN 122005878ACN-122005878-A

Abstract

The invention discloses a probe system for detecting Ox-LDL and application thereof, belonging to the technical field of Ox-LDL detection. The probe system for detecting Ox-LDL comprises a targeting molecule and a marker, wherein the targeting molecule is bound to the Ox-LDL at a target site through a specific binding effect, the marker comprises A-X-Y, wherein the A is a substituted or unsubstituted tetrazine group, the X can be default, the X can be a connector, the connector comprises at least one of an amide bond connector, an ether bond connector, a thioether bond connector and a PEG connector, and the Y comprises at least one of a radionuclide and a fluorescent element. The probe system combines the targeting specificity and the signal amplification effect, realizes the high-sensitivity and high-specificity in-vivo visualization of the important disease biomarker Ox-LDL, and has scientific research value and clinical transformation potential.

Inventors

  • SHEN ZHEN
  • ZHI XU
  • SHAO GUOQIANG

Assignees

  • 南京大学
  • 南京市第一医院

Dates

Publication Date
20260512
Application Date
20260204

Claims (10)

  1. 1. A probe system for detecting Ox-LDL, comprising a targeting molecule and a marker; the targeting molecule binds to the target site Ox-LDL by specific binding; the marker comprises A-X-Y, X being defaults; The A is a substituted or unsubstituted tetrazine group; The X can be a linker, and the linker comprises at least one of an amide bond type linker, an ether bond type linker, a thioether bond type linker and a PEG type linker; The Y comprises at least one of a radionuclide and a fluorescent element.
  2. 2. The probe system for detecting Ox-LDL according to claim 1, wherein the amide linkage linker is a metal chelator comprising at least one of DOTA, DTPA, NOTA, NODAGA, EDTA, resca, DFO, HEBCC, hynic.
  3. 3. The probe system for detecting Ox-LDL according to claim 1, wherein the radionuclide comprises at least one of 68 Ga、 64 Cu、 89 Zr、 18 F、 111 In、 99m Tc、 44 Sc; The fluorescent element comprises at least one near infrared dye selected from the group consisting of IR dye, cy dye, BODIPY dye, porphyrin and phthalocyanine dye, squaraine dye, cyanine analog and rhodamine derivative; the IR dye comprises at least one of IR780, IR808, IR820 and IR 1048; the Cy dye comprises at least one of Cy5, cy5.5, cy7 and Cy7.5; the BODIPY dye comprises at least one of BDP-650/670 and aza-BODIPY; the porphyrin and phthalocyanine dye comprises at least one of ZnPc, alPc and naphthalocyanine; the squaraine dye comprises at least one of SQ-1 and SQ-3; The cyanine analogues and rhodamine derivatives comprise at least one of Si rhodamine and Ox rhodamine.
  4. 4. The probe system for detecting Ox-LDL according to claim 1, wherein the targeting molecule is 1j-TCO, and the specific structural formula of 1j-TCO is as follows: 。
  5. 5. The probe system for detecting Ox-LDL according to claim 1, wherein the marker is IR780-MeTz, and the IR780-MeTz has the following structural formula: 。
  6. 6. The probe system for detecting Ox-LDL according to claim 1, wherein the marker has the following structural formula 68 Ga-DOTA-PEG 4 -MeTz, 68 Ga-DOTA-PEG 4 -MeTz: 。
  7. 7. The probe system for detecting Ox-LDL according to claim 1, wherein the working range of the probe system is 1-100. Mu. Mol, and the detection range of the target is 1-100. Mu.g/mL.
  8. 8. A composition comprising the probe system for detecting Ox-LDL according to any one of claims 1 to 7, which comprises the probe system for detecting Ox-LDL and a pharmaceutically acceptable carrier.
  9. 9. Use of the probe system for detecting Ox-LDL according to any one of claims 1 to 7 for preparing products for near infrared detection, PET, SPECT imaging of Ox-LDL.
  10. 10. Use of the probe system for detecting Ox-LDL according to any one of claims 1 to 7 for preparing an early diagnosis reagent for atherosclerosis and an early diagnosis reagent for fatty liver.

Description

Probe system for detecting Ox-LDL and application thereof Technical Field The invention relates to the technical field of Ox-LDL detection, in particular to a probe system for detecting Ox-LDL and application thereof. Background Lipoproteins are small particles composed of both lipids and proteins responsible for transporting lipids in the blood and delivering them to tissues. Low Density Lipoprotein (LDL) is a major carrier of cholesterol, its major lipid component being cholesterol ester, and also contains a small amount of free cholesterol. The major apolipoprotein in LDL is ApoB-100.LDL is in a spherical structure with a diameter of about 22 nm and a density in the range of 1.019 to 1.063 g/cm 3. These particles are heterogeneous in size, density and composition, and 2 to 38 subtypes have been identified, depending on the method of investigation. The composition of LDL subtypes and their distribution are subject to individual differences, determined by both genetic and environmental factors. Under physiological conditions, the human body maintains redox homeostasis. However, when Reactive Oxygen Species (ROS) production increases, components such as phospholipids, cholesterol esters, and polyunsaturated fatty acids in LDL are easily oxidized to form oxidized low-density lipoprotein (Ox-LDL), and small and dense LDL is more easily oxidized than large-particle LDL. Although the mechanism of action of Ox-LDL in vivo is not yet defined and the specific oxidative spatiotemporal character of LDL is still sought, there is increasing evidence that Ox-LDL is an important biomarker for cardiovascular disease. Studies have shown that Ox-LDL levels are positively correlated with coronary lesion severity, suggesting that high levels of Ox-LDL may lead to plaque destabilization by altering plaque composition, exacerbating inflammatory reactions, and promoting surface thrombosis. Traditional biological research relies on tissue extraction for analysis after animal sacrifice, which only can obtain a certain isolated snapshot in the life process, but cannot capture dynamic change information of key biomolecules in the living body real microenvironment under the condition of disease occurrence, development or drug intervention. The in-vivo probe can perform in-situ marking, amplifying and reporting on specific targets (such as proteins and nucleic acids) by utilizing specific molecular recognition (such as antibodies and small molecular ligands) or biological orthogonal reaction, so that people can see the real-time behaviors of the biological events under normal or pathological states in an in-vivo animal or human body, early, noninvasive and high-sensitivity visual positioning of lesions is realized in the living animal or human body, and a brand new technical path is opened for ultra-early intervention, surgical navigation and personalized medicine evaluation of diseases. In conclusion, it is of great scientific and practical importance to design an in-vivo probe detection system for Ox-LDL. Disclosure of Invention In view of the above problems of the prior art, the present invention provides a probe system for detecting Ox-LDL and an application thereof. The probe system is a 'pre-targeting-signal amplification' two-component design based on bioorthogonal reaction, comprising a targeting molecule that can specifically bind to the target site Ox-LDL, and a marker for achieving visual detection of the target region. The technical scheme of the invention is as follows: The first aspect of the present invention provides a probe system for detecting Ox-LDL, comprising a targeting molecule and a marker; the targeting molecule binds to the target site Ox-LDL by specific binding; the marker comprises A-X-Y, X being defaults; The A is a substituted or unsubstituted tetrazine group; The X can be a linker, and the linker comprises at least one of an amide bond type linker, an ether bond type linker, a thioether bond type linker and a PEG type linker; The Y comprises at least one of a radionuclide and a fluorescent element. Preferably, the amide bond type linker is a metal chelator, including at least one of DOTA, DTPA, NOTA, NODAGA, EDTA, resca, DFO, HEBCC, hynic. Preferably, the radionuclide comprises at least one of 68Ga、64Cu、89Zr、18F、111In、99mTc、44 Sc; The fluorescent element comprises at least one near infrared dye selected from the group consisting of IR dye, cy dye, BODIPY dye, porphyrin and phthalocyanine dye, squaraine dye, cyanine analog and rhodamine derivative; the IR dye comprises at least one of IR780, IR808, IR820 and IR 1048; the Cy dye comprises at least one of Cy5, cy5.5, cy7 and Cy7.5; the BODIPY dye comprises at least one of BDP-650/670 and aza-BODIPY; the porphyrin and phthalocyanine dye comprises at least one of ZnPc, alPc and naphthalocyanine; the squaraine dye comprises at least one of SQ-1 and SQ-3; The cyanine analogues and rhodamine derivatives comprise at least one of Si rhodamine and Ox rhodamine. Pr