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Tumor in-situ oxygen production sensitization photodynamic curative effect targeting penetration type nanometer diagnosis and treatment compound and preparation method thereof

A nano-composite, penetrating technology, applied in the field of medical materials

Active Publication Date: 2020-10-27
UNIV OF ELECTRONICS SCI & TECH OF CHINA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, these methods have not been able to improve the hypoxia inside the tumor at the same time.

Method used

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  • Tumor in-situ oxygen production sensitization photodynamic curative effect targeting penetration type nanometer diagnosis and treatment compound and preparation method thereof
  • Tumor in-situ oxygen production sensitization photodynamic curative effect targeting penetration type nanometer diagnosis and treatment compound and preparation method thereof
  • Tumor in-situ oxygen production sensitization photodynamic curative effect targeting penetration type nanometer diagnosis and treatment compound and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0044] A target-penetrating nanotherapeutic complex for in situ oxygen generation and enhanced photodynamic therapy of tumors, including GO-MnO based on graphene oxide 2 Composite oxygen-generating carrier,

[0045] The tumor-targeted homing penetrating peptide linked to the composite oxygen-generating carrier by chemical covalent linkage, and the peptide linked to the composite oxygen-generating carrier by π-π stacking, hydrophobic force, hydrogen bond or electrostatic interaction Photosensitizer, the specific preparation process is as follows:

[0046] The first step, synthesis of GO-MnO 2 Composite oxygen-generating carrier

[0047] 1 mL of poly(allylamine hydrochloride) (PAH) solution (concentration: 1 mg / mL) was added dropwise to 2 mL of graphene oxide solution (concentration: 0.5 mg / mL) under magnetic stirring conditions, and reacted overnight to obtain GO -PAH complex; 1mL potassium permanganate solution (8.4mg / mL) was added dropwise to the GO-PAH complex, stirred ov...

Embodiment 2

[0062] Example 2 GM@tLyP-1 / Ce6 In Vitro Oxygen Production, Singlet Oxygen Production Rate and MRI Imaging Performance Test

[0063] The performance of the target-penetrating nano-diagnosis and treatment compound prepared by the present invention is mainly evaluated by the following methods:

[0064] 1. Characterization of oxygen production performance

[0065] An equal amount of 100 mg of GM@tLyP-1 / Ce6 solution was reacted with 100 μM hydrogen peroxide solution at pH 6.5 and 7.4 respectively, and a blank control group was set. Use the JPBJ-608 portable dissolved oxygen analyzer to detect the oxygen content of the solution every 10s.

[0066] Such as Figure 6 a, in H 2 o 2 Solution (100μM)+GM@tLyP-1 / Ce6 group can quickly trigger the reaction to produce O 2 , and the rate of oxygen production increases significantly with the increase of acidity, which proves that the GM@tLyP-1 / Ce6 nanocomposite has a good oxygen production effect.

[0067] 2. Characterization of active ox...

Embodiment 3

[0074] Example 3 GM@tLyP-1 / Ce6 in vitro cytotoxicity, targeted endocytosis and penetration experiments

[0075] GM@tLyP-1 / Ce6 prepared according to the preparation method provided in Example 1, mouse breast cancer cells 4T1 were purchased from ATCC, and RPMI 1640 medium was used to culture 4T1 cells.

[0076] 1. Cytotoxicity experiment of GM@tLyP-1 vector

[0077] 4T1 cells in logarithmic growth phase were seeded in 96-well plates (density 1.0×10 4 per well), cultured for 24 hours. Remove the culture medium in the well plate, add different concentrations of GM@tLyP-1 (25.0, 50.0, 100.0, 150.0, 200.0, 250.0 μg / mL) into the well plate (repeat three wells for each concentration), and continue to cultivate 12h. Remove the cell culture medium and wash with PBS buffer three times. Add 100 μL of prepared CCK-8 working solution to each well and continue to incubate for 45 min. The absorbance value (OD value) at 450nm was detected by a microplate reader, and the cell survival rate...

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Abstract

The invention provides a tumor in-situ oxygen production sensitization photodynamic curative effect targeting penetration type nanometer diagnosis and treatment compound and a preparation method thereof. The nanometer diagnosis and treatment compound comprises three parts: a GO-MnO2 composite oxygen production type carrier adopting graphene oxide as a substrate, a tumor targeting homing penetrating peptide connected with the carrier, and a photosensitizer carried onto the carrier. The nano diagnosis and treatment compound has the functions of tumor targeted depth penetrability, tumor microenvironment responsive in-situ oxygen production and MRI / fluorescence imaging, and the photodynamic curative effect can be greatly improved.

Description

technical field [0001] The invention belongs to the technical field of medical materials, and in particular relates to a targeted penetrating nano-diagnosis and treatment compound for in situ oxygen generation of tumors to enhance photodynamic efficacy and a preparation method thereof. Background technique [0002] Photodynamic therapy (PDT) is a new type of non-invasive therapy for tumors. Its basic principle is to excite a photosensitizer accumulated in target cells or tissues by a laser with an appropriate wavelength, and undergo a photochemical reaction to make it interact with the tumor. Oxygen molecules react to form reactive oxygen species (Reactive oxygen species, ROS), thereby producing cytotoxicity to kill tumor cells and achieve the purpose of anti-tumor. Compared with other methods such as chemotherapy, photodynamic therapy has the advantages of lower toxicity, higher selectivity, minimal invasiveness and high efficiency. Since its clinical application in the 19...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K41/00A61K33/32A61K47/52A61K47/58A61K47/64A61K49/00A61K49/08A61K49/14
CPCA61K33/32A61K41/0057A61K41/0071A61K49/0002A61K49/0021A61K49/0056A61K49/08A61K49/14A61K47/52A61K47/58A61K47/64A61K2300/00
Inventor 吴春惠张映雪谢正鑫王易坤刘贻尧杨红李亭亭秦翔李顺
Owner UNIV OF ELECTRONICS SCI & TECH OF CHINA
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