Hemoglobin-photosensitizer reagent for photodynamic therapy of tumor and its application

A photodynamic therapy and hemoglobin technology, which is applied in the field of hemoglobin-photosensitizer reagents, can solve the problem that the therapeutic effect of tumor photodynamic therapy is not very satisfactory, and achieve the effects of significantly enhancing the curative effect, facilitating operation and promotion, and reducing the impact.

Active Publication Date: 2019-01-04
SHENZHEN INST OF ADVANCED TECH CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, in practical applications, the therapeutic effect of tumor photodynamic therapy is not very satisfactory.

Method used

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  • Hemoglobin-photosensitizer reagent for photodynamic therapy of tumor and its application
  • Hemoglobin-photosensitizer reagent for photodynamic therapy of tumor and its application
  • Hemoglobin-photosensitizer reagent for photodynamic therapy of tumor and its application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0041] An aqueous hemoglobin solution (5 mg / mL final concentration) was mixed with an indocyanine green solution (100 μg / mL final concentration). Pass pure oxygen into the mixed solution through the airway tube to oxygenate the hemoglobin, and the dissolved oxygen concentration in the solution reaches 35mg / L.

[0042] figure 1 Schematic diagram of computational analysis of the interaction between hemoglobin and indocyanine green molecules. The four heme molecules in hemoglobin can carry oxygen. According to the calculation and analysis of biomolecules, after the indocyanine green molecule is non-covalently combined with the hemoglobin molecule, the distances from the four oxygen-carrying sites are 17.3, 18.4, 21.3, and 25.4, respectively. Angstrom, the oxygen molecule is very close to the photosensitizer molecule, and the utilization rate of oxygen in the photodynamic reaction is improved.

[0043]Add the oxygenated hemoglobin-indocyanine green mixed solution (the concentrat...

Embodiment 2

[0046] MCF-7 tumor cells were inoculated overnight in a 96-well plate at a density of 5000 cells / well, and oxygenated hemoglobin (final concentration was 5 mg / mL, oxygenated to a dissolved oxygen amount above 30 mg / L) and indocyanine green (final Concentration of 100 μg / mL) mixed solution to replace the cell culture medium, incubate for 30 minutes, and then adjust the power and focus of the 808nm laser to make the light spot at 0.1W / cm 2 The power density irradiates the tumor area for 5 minutes for treatment. After the treatment, the cells were cultured for 24 hours, and the cell viability was analyzed.

[0047] For experimental results, see image 3 As shown, the groups from left to right in the figure are: untreated hemoglobin + indocyanine green (this group is a no-light group, and the following four groups are all treated with laser irradiation), indocyanine green (deoxygenated solution), deoxygenated Hemoglobin + indocyanine green, indocyanine green (oxygenated solution...

Embodiment 3

[0049] Inoculate MCF-7 tumor cells on the dorsal side of nude mice, when the transplanted tumor grows to a volume of 100mm 3 120 μL of a mixed solution of hemoglobin (final concentration: 15 mg / mL) and indocyanine green (final concentration: 500 μg / mL) was injected into the tumor, and 808 nm By adjusting the power and focus of the laser, the light spot can be adjusted at 0.1W / cm 2 The power density was irradiated to the tumor area for 30 minutes.

[0050] Figure 4 Cell necrosis analysis shown for enhanced photodynamic therapy with oxygenated hemoglobin. According to the observation of the treated nude mice, 6 days after the treatment, the tumor area was necrotic and scabbed, and the tumor growth was significantly inhibited.

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Abstract

The invention provides a hemoglobin-photosensitizer reagent used for tumor photodynamic therapy and application thereof. The hemoglobin-photosensitizer reagent is prepared from a hemoglobin and photosensitizer non-covalent binding material. The hemoglobin and photosensitizer non-covalent binding material is prepared according to the following method that a hemoglobin solution and a photosensitizer solution are mixed, mixed liquid is filled with oxygen, and the hemoglobin and photosensitizer non-covalent binding material filled with oxygen is obtained. By means of oxygen supply of hemoglobin, laser is adopted as a light source, irradiation is performed after photosensitizer and oxygen are enriched in tumor, the yield of active oxygen in photodynamic therapy can be greatly increased, tumor growth is inhibited, and the curative effect is remarkably enhanced.

Description

technical field [0001] The present invention relates to a hemoglobin-photosensitizer reagent for photodynamic therapy of tumors and its application, specifically, the present invention relates to a non-covalent combination reagent of hemoglobin and photosensitizer, which can be used for photodynamic therapy of tumors The method uses hemoglobin to provide sufficient oxygen to enhance the effect of photodynamic therapy, so as to inhibit the growth of tumor. Background technique [0002] There are many treatment methods for tumors, but at present the most basic and main methods are still surgery, radiotherapy and chemotherapy. Exploring new treatment methods with less toxic and side effects, or adding some auxiliary means on the basis of the current treatment methods, so as to improve the curative effect and reduce the toxic and side effects, is an urgent problem to be solved in the current tumor treatment. [0003] In recent years, photodynamic therapy has attracted widesprea...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K41/00A61N5/06A61K47/64A61P35/00
CPCA61K41/0057A61K41/0071A61N5/06
Inventor 蔡林涛罗震宇郑明彬赵鹏飞陈泽倪大鹏
Owner SHENZHEN INST OF ADVANCED TECH CHINESE ACAD OF SCI
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