Photosensitizer targeting tumor expressing urokinase receptor, preparation method and use thereof

A technology for photosensitizers and uses, applied in the field of tumor photosensitizers and their preparation, can solve the problems of low water solubility and poor tumor targeting of metal phthalocyanine photosensitizers, and achieve good selectivity, high selectivity, and simple preparation Effect

Active Publication Date: 2019-05-28
FUJIAN INST OF RES ON THE STRUCTURE OF MATTER CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] Aiming at the shortcomings of low water solubility and poor tumor targeting of metal phthalocyanine photosensitizers, the invention provides a preparation method for improving its water solubility and enhancing its tumor targeting

Method used

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  • Photosensitizer targeting tumor expressing urokinase receptor, preparation method and use thereof
  • Photosensitizer targeting tumor expressing urokinase receptor, preparation method and use thereof
  • Photosensitizer targeting tumor expressing urokinase receptor, preparation method and use thereof

Examples

Experimental program
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Effect test

Embodiment 1

[0034] Example 1: Preparation of Zinc Phthalocyanine-Urokinase Conjugate (ATF-ZnPc)

[0035] Step 1: Synthesis of ZnPc-CO-NH-(CH 2 ) 2 -NH 2

[0036]Dissolve 9.3 mg (0.015 mmol) of β-monocarboxyl substituted zinc phthalocyanine and 23.1 mg (0.06 mmol) of benzotriazole-N,N,N',N'-tetramethyluronium hexafluorophosphate (HBTU) Add 93 μL N,N-diisopropylethylamine (DIEA) to 1.5 mL N,N-dimethylformamide (DMF), and stir for 30 min at room temperature in the dark. Add excess N-BOC-1,2-ethylenediamine, and stir overnight at room temperature in the dark. The resulting reaction solution was freeze-dried to obtain a solid that was ZnPc-CO-NH-(CH 2 ) 2 -NH-Boc. React it with 90% trifluoroacetic acid (TFA) for 4 hours, add 4 times the volume of 4M sodium hydroxide solution, and precipitate; centrifuge to discard the upper clear night, and dissolve the precipitate with N,N-dimethylformamide (DMF). Further purification by high performance liquid chromatography (SinoChrom ODS-BP column,...

Embodiment 2

[0043] Example 2: Zinc Phthalocyanine-Urokinase Conjugate (ATF-ZnPc) can target tumor cells with high expression of urokinase receptor. In this example, normal human embryonic lung fibroblast HELF with low expression of urokinase receptor (Shanghai Institute of Cell Biology, Chinese Academy of Sciences) and human leukemia cell U937 with high expression of urokinase receptor (Shanghai Institute of Cell Biology, Chinese Academy of Sciences) ) and human lung cancer cells H1299 (Shanghai Institute of Cell Biology, Chinese Academy of Sciences) as examples.

[0044] The above three kinds of cells were selected for the experiment: normal human embryonic lung fibroblast HELF with low expression of urokinase receptor, human leukemia cell U937 and human lung cancer cell H1299 with high expression of urokinase receptor. The specific experimental steps are as follows: (1) Cell culture conditions: at 37°C, 5% CO 2 RPMI-1640 medium containing 10% fetal bovine serum Culture; (2) In vitro ...

Embodiment 3

[0045] Example 3: Zinc phthalocyanine-urokinase conjugate (ATF-ZnPc) can be used for tumor imaging in vivo and in vitro.

[0046] Tumor cell imaging in vitro: Normal human embryonic lung fibroblast HELF with low expression of urokinase receptor and liver cancer cell H22 with high expression of urokinase receptor were taken as examples.

[0047] Tumor cell H22 (high expression of uPAR) and normal human embryonic lung fibroblast HELF (low expression of uPAR) were selected as in vitro imaging cells, cultured and passaged according to conventional cell culture methods. Add 2ml cell suspension (5×10 4 Cells / ml) and 2 μM ATF-ZnPc were incubated for 4 hours, and then added with DAPI nuclear staining solution for incubation. After 5 minutes, remove the staining solution and use Olympus FluoView TM FV1000 laser confocal microscope was used to acquire images with laser scanning of 670nm (ATF-ZnPc) and 405nm (DAPI). result( Figure 4 ) showed that zinc phthalocyanine-urokinase conjug...

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Abstract

The invention relates to the field of biological medicines, in particular relates to targeted therapy of tumors and provides a photosensitizer for targetedly expressing tumors of a urokinase receptor and use of the photosensitizer. The photosensitizer is a covalent conjugate of phthalocyanine zinc (ZnPc) and a recombinant urokinase amino-terminal fragment (ATF), has high selectivity for expressing tumor cells of the urokinase receptor, can be used for in vitro and vivo tumor imaging and photodynamic therapy and has potential application prospects.

Description

technical field [0001] The invention relates to the field of biomedicine, more specifically to targeted therapy of tumors, and to a photosensitizer targeting tumors expressing urokinase receptors, a preparation method and application thereof. Background technique [0002] Although tumor is an ancient disease, it was still a relatively rare disease in the world until the beginning of last century. For nearly half a century, the incidence of tumors has been increasing year by year, and its status in the medical field has become more and more important. At present, tumor has become a frequently-occurring and common disease, one of the main causes of human death, and a serious threat to human health. According to its current incidence trend, it is estimated that the annual number of new cancer patients in the world will reach 15 million in 2020, and cancer is becoming the number one killer of human beings in this century. [0003] Photodynamic therapy (PDT) is a method to trea...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K41/00A61K49/00A61K47/64A61P35/00A61P35/02
Inventor 黄明东陈卓徐芃陈锦灿周山勇胡萍陈学元
Owner FUJIAN INST OF RES ON THE STRUCTURE OF MATTER CHINESE ACAD OF SCI
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