Near-infrared driven self-oxygen-supply compound, and preparation method and application thereof

A complex, near-infrared technology, applied in the directions of medical preparations, pharmaceutical formulations, and drug combinations containing active ingredients, can solve the problems of difficult photodynamic therapy, complex mechanism, oxygen supply, etc., and achieve obvious photodynamic therapy effect. , high biosafety effect

Active Publication Date: 2020-09-29
HEBEI UNIVERSITY
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, natural matrix-free hemoglobin cannot be directly used as a blood substitute, because hemoglobin has a high colloid osmotic pressure in plasma, and the half-life of the tetramer in the circulation is only 2-4 h, and then rapidly decomposes into dimers and monomers and filtered from the kidneys
At the same time, because the free hemoglobin tetramer molecule and its decomposition products can penetrate the vascular endothelium and enter the organ and tissue interstitium, it will cause serious side effects
[0006] In addition, the method of trying to prevent oxygen consumption by cutting off the mitochondrial respiratory chain of tumor cells has a complex mechanism and is limited by the concentration of the drug itself, and it is also difficult to provide enough oxygen for photodynamic therapy.

Method used

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  • Near-infrared driven self-oxygen-supply compound, and preparation method and application thereof
  • Near-infrared driven self-oxygen-supply compound, and preparation method and application thereof
  • Near-infrared driven self-oxygen-supply compound, and preparation method and application thereof

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Embodiment 1

[0050] The used blue-green algae of the present invention are purchased from Chinese Academy of Sciences Freshwater Algae Species Bank (Latin species name: Synechococcus7942 , number FACHB-805, hereinafter referred to as S), sterilize the 50 mL culture bottle prepared in advance, then add the prepared culture medium (the configuration method is as follows), and transfer the purchased strains to the Erlenmeyer flask in the ultra-clean bench , seal the bottle mouth with sealing film and kraft paper to ensure aseptic culture. The Erlenmeyer flask was placed in a light incubator for 2-3 days of cultivation, the cultivation temperature was 25°C, the light condition was 1000-2000Lux, and the time was set to 12h day / 12h night.

[0051] The configuration method of BG-11 medium: add 0.15g NaNO 3 , 0.004g K 2 HPO 4 , 0.0075g MgSO 4 •7H 2 O, 0.0036g CaCl 2 •7H 2 O, 0.002g Na 2 CO 3 , 0.006g citric acid, 0.006g ferric ammonium citrate, 0.0001g disodium EDTA, dissolved in 99mL th...

Embodiment 2

[0060] The near-infrared-driven self-oxygen complex S-UCNP-Ce6 was synthesized by the following method.

[0061] (1) Upconversion nanoparticles (UCNPs) (NaYF 4 :Yb,Er) synthesis

[0062] Weigh 0.205gYCl respectively 3 , 0.056gYbCl 3 , 0.005gErCl 3 In a 100mL three-necked flask, add 15mL of octadecene and 10mL of oleic acid, vacuum the inside of the three-necked flask and fill it with N 2 . Then the solution was heated to 150° C. and kept stirring for 30 minutes. After the reaction was completed, the heating was turned off, and the next step was performed when the temperature dropped to 50° C. Weigh 0.148gNH 4 F in 7.5mL of methanol, 0.1g of NaOH in 2.0mL of methanol, sonicated for about 30min until completely dissolved. The dissolved solution was mixed and quickly put into the above-mentioned three-necked flask, and kept stirring at 50°C for 30 min. Then the temperature was raised to 100°C, and when there were no bubbles in the flask, the vacuum was drawn again and mix...

Embodiment 3

[0077] Extracellular production of S-UCNP-Ce6 under near-infrared light 1 o 2

[0078] Put S-UCNP-Ce6 into a 50mL three-neck flask containing 25mL of PBS solution, use a double-row tube to evacuate, and fill it with N 2 with CO 2 of mixed gas. Take 9,10-Anthracenediyl-bis(methylene)-dimalonic acid (ABDA) as 1 o 2 To detect the probe, draw the solution with a long-needle syringe sequentially when the 980nm exciter is illuminated for 0min, 2min, 5min, 10min, 15min, and 20min, and use a UV-visible spectrophotometer to detect the change of the characteristic absorption peak of ABDA in the range of 300nm-450nm Trend, and compared with UCNP-Ce6 group.

[0079] Such as Figure 8 As shown, even in the hypoxic environment, S-UCNP-Ce6 obviously produces 1 o 2 , however in UCNP-Ce6 1 o 2 There is no significant change in the concentration of cyanobacteria, which proves that cyanobacteria can produce oxygen and have obvious production under the action of photosensitizer 1 o 2...

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Abstract

The invention provides a near-infrared driven self-oxygen-supply compound, and a preparation method and application thereof. The compound comprises a photosensitizer, up-conversion nanoparticles and carrier blue-green algae; the photosensitizer and the up-conversion nanoparticles are loaded on the carrier blue-green algae; when near-infrared exciting light is applied for irradiation, the up-conversion nanoparticles can convert the near-infrared exciting light into multiple sections of exciting light with different wavelengths, wherein the visible light part is absorbed by blue-green algae, andgenerates a large amount of oxygen; and the exciting light at 650-700 nm enables the photosensitizer to generate singlet oxygen in the presence of oxygen. The compound has relatively high biologicalsafety to a body, has an obvious photodynamic therapy effect on malignant melanoma mice, solves the problem that photodynamic therapy is invalid to a tumour hypoxic region, provides a new scientific basis for radical treatment of tumours, and has important scientific significance.

Description

technical field [0001] The invention relates to the photodynamic therapy of malignant hypoxic tumors, in particular to a near-infrared-driven self-oxygen compound and its preparation method and application. Background technique [0002] Photodynamic therapy (PDT) is a new technology for diagnosing or treating tumors by photochemical reactions generated by laser irradiation on photosensitizers. The basic elements are oxygen, photosensitizers and light. Compared with traditional radiotherapy and chemotherapy, photodynamic therapy has many advantages such as good selectivity, low toxicity, small trauma, and less drug resistance. After more than 20 years of development, anti-tumor photodynamic therapy has become increasingly mature. However, since photodynamic therapy is oxygen-dependent, the hypoxic region of the tumor becomes a blind area of ​​photodynamic therapy, which severely limits the therapeutic effect of photodynamic therapy on solid tumors. [0003] Hyperbaric oxyge...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K41/00A61P35/00
CPCA61K41/0071A61P35/00
Inventor 李振华张英华刘会芳张金超
Owner HEBEI UNIVERSITY
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