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Nano lipidosome for sensitizing tumor radiotherapy and application

A nano-liposome and tumor radiotherapy technology, applied in the medical field, can solve acute glomerular necrosis and other problems, achieve high biocompatibility, effective tumor targeting, and increase the amount of active oxygen

Inactive Publication Date: 2018-12-21
ZHEJIANG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the hemoglobin molecule is a tetramer that rapidly dissociates into two dimers, which can lead to acute glomerular necrosis and renal failure

Method used

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  • Nano lipidosome for sensitizing tumor radiotherapy and application
  • Nano lipidosome for sensitizing tumor radiotherapy and application
  • Nano lipidosome for sensitizing tumor radiotherapy and application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0016] Example 1 Synthesis and characterization of hemoglobin-liposome

[0017] Hemoglobin-liposomes were prepared by water-in-oil-in-water double emulsion, specifically through the following steps: 150 mg of CTAB was added to hemoglobin aqueous solution (15 mg per ml, 2 ml), followed by ultrasonic dispersion for 3 minutes. This mixture serves as the aqueous phase in the subsequent emulsion. This was mixed with lecithin 80 (60 mg) and distearoylphosphatidylethanolamine-polyethylene glycol 2000 (9 mg) dissolved in chloroform (3.5 mL) under stirring to give a water-in-oil form Emulsion, then, the remaining 100 ml of water (as the external water phase) was added to the water-in-oil emulsion to form a water-in-oil-in-water double emulsion. The final emulsion system was vacuum evaporated to remove organic solvents and obtain hemoglobin-liposomes. It was freeze-dried for subsequent use.

[0018] Before use, the hemoglobin-liposome solution was subjected to oxygen for 15 minutes t...

Embodiment 2

[0021] 1. Materials and methods

[0022] (1) Material

[0023] Distearoylphosphatidylethanolamine-polyethylene glycol 2000 and lecithin-80 were obtained from Lipoid GmbH (Ludwigshafen, Germany). Human hemoglobin, cetyltrimethylammonium bromide, Hoechst 33342 and MTT reagent were obtained from Sigma-Aldrich Company (St Louis, MO). The hypoxia marker Hypoxyprobe-1 plus kit was obtained from Hypoxyprobe (Burlington MA, USA). β-actin antibody, anti-mouse IgG, anti-rabbitIgG, reactive oxygen species detection kit, BCA protein concentration determination kit, RIPA lysate, and protease inhibitor cocktail were obtained from Beyotime Institute of Biotechnology (Jiangsu, China) . VEGF antibody, HIF-1α antibody, γ-H2AX antibody, TUNEL antibody and Ki67 antibody were obtained from Wuhan Sanying Biotechnology Co., Ltd. (Hubei, China). Cell membrane fluorescent probes DiD and DiR were from Life Technologies Biotechnology, USA. RPMI, DMEM, FBS, penicillin, and streptomycin were purchase...

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Abstract

The invention provides nano lipidosome for sensitizing tumor radiotherapy, in particular to hemoglobin-lipidosome which is obtained by generating complex emulsion in an oil-in-water manner and then removing an organic solvent through evaporation. The lipidosome can provide stable and safe oxygen supply, can realize the controlled release on a tumor part, can alleviate the low-oxygen state of a tumor micro environment, and can overcome the resistance of the tumor to the radiotherapy. By virtue of intravenous injection, the hemoglobin-lipidosome has effective tumor targeting performance; and moreover, HIF-1alpha and VEGF levels inside the tumor are lowered, and the low-oxygen environment of the tumor is apparently improved. Under X rays, the active oxygen amount of the tumor is apparently increased. By applying the hemoglobin-lipidosome, the radiotherapy effectiveness can be significantly reflected in a living animal model with different radiotherapy resistances. The nano lipidosome is used as an oxygen carrier for sensitizing tumor radiotherapy and is extremely high in bio-compatibility, and the antitumor activity can be significantly improved.

Description

technical field [0001] The invention belongs to the field of medicine and relates to a liposome based on a bionic oxygen delivery carrier, in particular to a nano-liposome for sensitizing tumor radiotherapy and its application as an oxygen-carrying carrier for sensitizing tumor radiotherapy. Background technique [0002] Hypoxia is a common pathophysiological feature in a variety of tumors and is the result of an imbalance between oxygen supply and consumption. Tumor hypoxia has been shown to be associated with poor clinical outcomes, including radiation therapy. Under X-rays, the DNA inside the cell is transformed into DNA free radicals, which then combine with oxygen, causing breakage of the DNA double strands and permanent damage. However, DNA fragments may be repaired under hypoxic conditions. Therefore, in order to improve the effectiveness of radiotherapy, it is crucial to adjust the hypoxic state of the tumor. For example, hyperbaric oxygen therapy increases the ef...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/42A61K9/127A61P35/00
CPCA61K9/0019A61K9/1271A61K38/42A61P35/00
Inventor 游剑裘云庆楼燕郭晓萌
Owner ZHEJIANG UNIV
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