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Photodynamics therapy complex as well as preparation method and application thereof

A compound and compound technology, applied in the field of photodynamic therapy compound and its preparation, can solve the problems of restricting wide application, reducing the effect of photodynamic therapy, and limiting the effect of photodynamic therapy, so as to increase the production of active oxygen and solve the problem of active oxygen Reduced oxygen production, avoiding normal tissue damage

Active Publication Date: 2018-08-21
INST OF CHEM CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although photodynamic therapy is a promising treatment method, there are still some factors that limit its wide application in clinic
The absorption and scattering effects of biological tissues prevent external light sources from reaching deep tumor tissues, and the need for external light sources limits the therapeutic effect of photodynamic therapy in deep tumor tissues
In addition, the tumor microenvironment often presents a hypoxic state, which significantly reduces the effect of photodynamic therapy for anti-tumor therapy
At present, researchers at home and abroad have only solved one of the problems, but the research work that can solve these two problems at the same time and fully exert the anti-tumor effect of photodynamic therapy has not been reported.

Method used

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  • Photodynamics therapy complex as well as preparation method and application thereof
  • Photodynamics therapy complex as well as preparation method and application thereof
  • Photodynamics therapy complex as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0065] Embodiment 1, the preparation of photodynamic therapy compound

[0066] (1), preparation of nanoparticles composed of compounds shown in formula I and formula II

[0067] Dissolve 0.5 mg of the compound shown in Formula I (n is 560-960) and 0.25 mg of the compound shown in Formula II in 5 mL of tetrahydrofuran and use ultrasound to dissolve it completely, then drop the above tetrahydrofuran solution into 15 mL of ultrapure water and ultrasonic dispersion. After ultrasonic dispersion with 50W power for 5 minutes, continue to stir in a fume hood at 25°C overnight to obtain nanoparticles composed of compounds represented by formula I and formula II, and then filter through a 0.22 μm filter membrane to obtain the above target nanoparticles NPs in the filtrate.

[0068]

[0069] (2), preparation of nanoparticles modified by bovine hemoglobin

[0070] Add 0.3 mg of NHS and 0.6 mg of EDC to the filtrate obtained above, react in PBS buffer solution with pH = 7.4 at 37 ° C ...

Embodiment 2

[0076] Embodiment 2, the characterization of photodynamic therapy compound

[0077] (1) Characterization of particle size and zeta potential

[0078] The obtained nanoparticles NPs ( figure 1 ) and photodynamic therapy complex Hb-NPs@liposome ( image 3 ) structure for characterization. The above-mentioned bovine hemoglobin-modified nanoparticles Hb-NPs were characterized by a dynamic light scattering instrument for surface charge changes ( figure 2 ).

[0079] From figure 1 It can be seen that the nanoparticles NPs are uniformly distributed, spherical particles, and the hydration radius is about 20nm.

[0080] From figure 2 It can be seen from the figure that after the modification of bovine hemoglobin, the surface charge of the nanoparticles changed from -40mV to -17mV, indicating that the modification was successful.

[0081] From image 3 It can be seen that the photodynamic therapy complex Hb-NPs@liposome is uniformly spherical, and the hydration radius is about...

Embodiment 3

[0086] Example 3. The photodynamic therapy complex is used for tumor cell killing under the activation of chemical activators

[0087] (1) Determination of bioluminescent energy transfer spectroscopy between luminol and Hb-NPs

[0088] Add 20 μL of 20 mM luminol and 150 μL of 45 mg / mL Hb-NPs to 805 μL of pH9.0 sodium carbonate buffer, vortex for 5 s, add 25 μL of 20 mM hydrogen peroxide aqueous solution for 2 s and measure the luminescence spectrum immediately, the spectral range is 300 nm to 700 nm. See Figure 5 .

[0089] From Figure 5 It can be seen that efficient energy transfer can occur between luminol and Hb-NPs.

[0090] (2) Determination of active oxygen

[0091] Activation of reduced 2,7-dichlorofluorescein (DCFH): add 2mL 0.01M NaOH to 500μL 2,7-dichlorofluorescein diethyl ester (DCFH-DA), let it stand at room temperature for 30min, then add 10mL phosphate buffer solution (25mM, pH=7.4), mix well and store in dark place on ice until use.

[0092] Add 90 μL o...

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Abstract

The invention discloses a photodynamics therapy complex as well as a preparation method and application thereof. The photodynamics complex is composed of nanoparticles, hemoglobin and a phospholipid layer, wherein the nanoparticles are self-assembled by compounds shown as formulas I and II shown in the description; the hemoglobin is modified on the surface of the nanoparticles; the phospholipid layer coats the hemoglobin and the nanoparticles. The complex can serve as an internal luminous source under chemical small molecule activation and provide enough oxygen, and the reactive oxygen yield is improved. Compared with the traditional photodynamics therapy, the photodynamics therapy complex disclosed by the invention is capable of treating deep tumor tissues, and solves the problem that thereactive oxygen yield is reduced due to hypoxia inside the tumor while avoiding a condition that normal tissues are injured due to long time irradiation of an external light source. The photodynamicstherapy complex disclosed by the invention has application value in clinic treatment of tumors.

Description

technical field [0001] The invention belongs to the field of photodynamic therapy, and relates to a photodynamic therapy compound and its preparation method and application. Background technique [0002] As a new type of treatment, photodynamic therapy has been applied in the clinical treatment of various tumors, ophthalmology and skin-related diseases. Photodynamic therapy has three important components, namely photosensitizer, light source and oxygen molecules. Under the excitation of a light source with a suitable wavelength, the photosensitizer can transfer the absorbed energy to the surrounding oxygen molecules to generate cytotoxic reactive oxygen species to kill cells. Although photodynamic therapy is a promising treatment method, there are still some factors that limit its wide application in clinic. The absorption and scattering effects of biological tissues prevent external light sources from reaching deep tumor tissues, and the need for external light sources li...

Claims

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Application Information

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IPC IPC(8): A61K41/00A61K9/51A61K47/24A61K31/502A61K31/765A61K33/40A61K47/64A61K47/69A61P35/00
CPCA61K9/5123A61K31/502A61K31/765A61K33/40A61K41/00A61K41/0057A61K47/6445A61K47/6933A61P35/00A61K2300/00
Inventor 王树蒋林冶任雪芹刘礼兵吕凤婷
Owner INST OF CHEM CHINESE ACAD OF SCI
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