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Targeted sonosensitizer compound for sonodynamic therapy and application of targeted sonosensitizer compound

A sonosensitizer and sonodynamic technology, applied in the field of medicine, can solve the problem that the therapeutic effect needs to be further improved, and achieve the effect of excellent killing effect, improving physical and chemical properties, and reducing toxicity

Pending Publication Date: 2022-01-14
上海释康企业管理咨询合伙企业(有限合伙)
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

At present, the methods of clinical treatment of tumors are mainly surgery, radiotherapy, chemotherapy, immunotherapy, traditional Chinese medicine and their combinations. However, the existing clinical treatment methods have considerable limitations, and the therapeutic effect needs to be further improved.

Method used

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  • Targeted sonosensitizer compound for sonodynamic therapy and application of targeted sonosensitizer compound
  • Targeted sonosensitizer compound for sonodynamic therapy and application of targeted sonosensitizer compound
  • Targeted sonosensitizer compound for sonodynamic therapy and application of targeted sonosensitizer compound

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0045] Preparation of quantum dot-sonosensitizer complex:

[0046] Quantum dots (Qdot 705ITKTM Amino, PEG) coated with double-terminal amino polyethylene glycol are selected. This amino QD is composed of a CdSeTe core and a ZnS shell, and then a layer of non-toxic SiO is coated on its outer layer. 2 Nano film, fluorescence peak at 696nm. When the pH value is 7 to 9, the hydroxysuccinimide ester reacts with the amino bond of the amino quantum dot (amino QD) to form a QD-maleimide complex. The thiol group of cysteine ​​in the CD105 joint peptide reacts to finally generate functionalized quantum dots linked to CD105. On the basis of functionalized CD105 quantum dots, a sonosensitizer (hematoporphyrin) approved by the State Food and Drug Administration for clinical trials was selected, and the sonosensitizer (blood porphyrin) was achieved through covalent bonds, hydrogen bonds, and π-π* interactions. Porphyrin) and the connection of this functional quantum dot.

[0047] At the ...

Embodiment 2

[0050] Using co-incubation method, the quantum dot-sound sensitizer complexes prepared in Example 1 were respectively co-cultured with 7 kinds of tumor cells, and treated with ultrasonic irradiation. Wherein, the dosage of the quantum dot-sound sensitizer complex is 30-100 μg / mL, specifically 50 μg / mL, and the irradiation time is 9 minutes.

[0051] Seven types of tumor cells are MDA-MB-231 (human breast cancer cells), SGC7901 (human gastric cancer cells), SKOV3 (human ovarian cancer cells), SGC996 (human gallbladder cancer cells), HCC827 (human non-small cell lung cancer cells) , PC3 (human prostate cancer cells), 8305C (human thyroid cancer cells).

[0052] Cell apoptosis was detected by PI staining method, and the experimental results were as follows: figure 1 , figure 2 As shown, under the action of ultrasonic irradiation, the quantum dot-sound sensitizer complex has excellent killing effect on 7 kinds of tumor cells, and after a single ultrasonic irradiation treatment,...

Embodiment 3

[0053] Example 3 Cytotoxicity Experiment

[0054] The quantum dot sound sensitizer complex (10 μg / mL) described in Example 1 was used to co-incubate with MDA-MB-231, and the incubation time was 0, 6, 12, 24, 48, and 72 h.

[0055] The results showed no significant difference in cytotoxicity compared to initial, see image 3 .

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Abstract

The invention discloses a targeted sonosensitizer compound for sonodynamic therapy and application of the targeted sonosensitizer compound. The targeted sonosensitizer compound comprises a marker and a sonosensitizer, the marker and the sonosensitizer are simultaneously grafted to a corresponding target molecule to realize specific identification of the target molecule; after being irradiated by sound waves, the sonosensitizer is subjected to a sonochemical reaction to generate reactive oxygen substances with cytotoxicity, so that cells or tissues are damaged. The method has the following advantages that the physical and chemical properties of quantum dots and the sonosensitizer are improved, and the quantum dots and the sonosensitizer are simultaneously and directionally transported to a focus, so that the concentration of the sonosensitizer in the focus is improved; the sonosensitizer can become a cavitation nucleus in liquid, the cavitation threshold is reduced, the sonosensitizer is directly located in cavitation bubbles, and the free radical yield is increased; the quantum dots and the sonosensitizer are simultaneously grafted to the target molecules, and under the sonodynamic effect, the quantum dots and the sonosensitizer have a remarkable killing effect on various tumor blood vessels and the targeted molecules for targeted treatment of tumors and even bacteria, viruses and the like, and have important clinical significance.

Description

technical field [0001] The invention relates to the field of medical technology, and mainly relates to a novel simultaneous grafting of target molecular dot quantum dots and sound sensitizers for precise treatment of tumor blood vessels, tumors and targeted molecular diseases. Background technique [0002] Malignant tumors seriously threaten human health. According to the report on tumor diseases in China, malignant tumors have become the second largest cause of death among residents in China in 2018. Tumor treatment is one of the most concerned and important research fields in current clinical medicine. At present, the methods of clinical treatment of tumors mainly include surgery, radiotherapy, chemotherapy, immunotherapy, traditional Chinese medicine and their combinations. However, the existing clinical treatment methods have considerable limitations, and the therapeutic effect needs to be further improved. Therefore, there is an urgent need for new and more effective m...

Claims

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Application Information

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IPC IPC(8): A61K41/00A61K47/69A61P35/00A61P31/00A61P29/00A61P37/02
CPCA61K41/0033A61K41/0028A61K47/6923A61P35/00A61P31/00A61P29/00A61P37/02
Inventor 郝良适郝长宁
Owner 上海释康企业管理咨询合伙企业(有限合伙)
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